Treatment of herpes simplex with a combination of valacyclovir and famciclovir.

Abstract

The present disclosure provides compositions and methods for preventing HSV infection in HSV-seronegative individuals and for treating and preventing recurrence in HSV-seropositive individuals.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 810,074, filed February 25, 2019. See U.S. Provisional Patent Application No. 62 / 021,589, filed July 7, 2014, U.S. Patent Application No. 14 / 793,550, filed July 7, 2015, issued as U.S. Patent No. 10,052,329, and pending U.S. Patent Application No. 16 / 044,276, filed July 24, 2018, which are incorporated by reference in their entireties. All documents cited herein or during the prosecution ("application cited documents") and all documents cited or referenced in the application cited documents, and all documents cited or referenced herein ("specification cited documents") and all documents cited or referenced in the specification cited documents, together with any manufacturer's instructions, manuals, product specifications, and product sheets referred to herein or in any document incorporated by reference herein, are incorporated herein by reference and may be used in the practice of this invention. More specifically, all referenced documents are incorporated by reference to the same extent as if each individual document was specifically and individually indicated to be incorporated by reference.

[0002] Technical Field The present invention relates generally to combinations of compounds with antiviral activity, and more specifically, antiherpetic properties. The present invention provides compositions of matter and methods of use for preventing and treating human herpes virus infections, which in turn may lead to other medical conditions. [Background technology]

[0003] A typical feature of alpha, beta, and gamma human herpesviruses is that they all establish latent infections. These viral infections are widespread worldwide. The consequences of these infections range from asymptomatic disease (i.e., seropositivity) to recurrent and / or severe episodes of symptoms caused by active disease. Some of these herpesvirus infections have devastating consequences, such as life-threatening encephalitis in newborns and immunocompromised patients. Classical nucleoside analogs are useful for treating herpesvirus-associated diseases, including varicella-zoster virus (i.e., VZV) and, to a lesser extent, Epstein-Barr virus (i.e., EBV) and cytomegalovirus (i.e., CMV), as well as HSV-1 and HSV-2.

[0004] As with all herpes viruses, once a virus infects a patient, it establishes a latent infection that is not cleared by the immune system, even with the aid of antiviral drugs such as valacyclovir or famciclovir. These antiviral drug compounds, prescribed and administered as monotherapy (i.e., monotherapy), have been shown to reduce the level of viremia in herpes simplex virus infections; however, even at high doses and over long treatment durations, these drugs do not completely prevent the common recurrent outbreaks of herpes virus infection symptoms. Viral shedding is also common, and this shedding can often subclinically facilitate the transmission of herpes viruses and the spread of disease to more individuals. Monotherapy, even at high doses and for extended periods, cannot achieve the long-term viral suppression of herpes infections necessary to stop outbreaks or prevent transmission to other individuals. In fact, long-term suppressive treatment with valacyclovir has been shown to reduce the risk of transmission by only 46%. This treatment outcome is in stark contrast to anti-HIV therapy, which can achieve sustained viral suppression and reduce the risk of transmission by nearly 100%. Currently, monotherapy is the standard of care for preventing herpes outbreaks and viral transmission. Given the very limited efficacy of monotherapy, there is a clear need for stronger protection against outbreaks and viral transmission that can be achieved through combination therapy of herpes infections. The use of antiviral drugs used in novel combinations could increase drug efficacy or perhaps provide equivalent antiviral effects with reduced dosages, thereby potentially reducing or limiting the risks associated with drug toxicity.

[0005] Recent studies suggest that herpesviruses, such as herpes simplex virus types 1 and 2 (i.e., HSV-1 and HSV-2), Epstein-Barr virus (i.e., EBV), human cytomegalovirus (i.e., HCMV), varicella-zoster virus (VZV, i.e., varicella-zoster, human herpesvirus 3), Kaposi's sarcoma-associated virus (i.e., KSHV, HHV-8), and human herpesviruses-6 and -7 (i.e., HHV-6, HHV-7), play a contributing role in causing a wide variety of diseases, including neonatal herpes, herpes encephalitis, Alzheimer's disease, senile dementia, multiple sclerosis, systemic lupus erythematosus (i.e., SLE), rheumatoid arthritis, juvenile idiopathic arthritis (i.e., JIA), inflammatory bowel disease (i.e., IBD), celiac disease, type 1 diabetes, and mononucleosis, among others. Summary of the Invention

[0006] Herpes simplex virus (HSV) recurs in many infected individuals, manifesting as cold sores and / or genital herpes, both of which are often painful and embarrassing. HSV also has significant public health consequences, as HSV infection increases the risk of human immunodeficiency virus (HIV) infection by two to three times, and exposure to HIV shortly after HSV infection increases the risk by eight times. Therefore, addressing the HIV epidemic requires addressing the HSV epidemic as well.

[0007] During primary infection, HSV infects epithelial cells of the skin and mucosal surfaces. The virus then travels along nerve axons to the dorsal root ganglia, where latency is established and the virus becomes dormant and hides from the immune system. These nerve cells therefore serve as reservoirs for latent virus. Upon reactivation, the virus migrates from the dorsal root ganglia back to the skin. This is called viral shedding, and the virus is detectable on epithelial surfaces. Viral reactivation can be asymptomatic or can cause lesions and ulcers. In either case, the virus can be transmitted to a new host. Most HSV-2 transmission occurs during asymptomatic shedding. Conventional methods for reducing HSV transmission through sexual contact include the use of a physical barrier, such as a condom, between HSV-seropositive and HSV-seronegative individuals. Condom use is effective in preventing some sexually transmitted diseases, but in the case of HSV, the site of infection may be outside the area protected by the condom. If viral shedding occurs at a site outside the condom area, skin-to-skin contact during viral shedding is sufficient for HSV transmission, and transmission may occur even with correct condom use.

[0008] Clinical treatment of HSV has shifted from a focus on acute treatment of symptomatic outbreaks (e.g., treatment of lesions) to reducing the frequency of symptomatic outbreaks and, therefore, viremia and viral shedding in seropositive individuals. This has led to the development of suppressive therapy, in which seropositive individuals attempt to maintain low levels of HSV antiviral drugs in their bloodstream to potentially reduce the number of outbreaks and reduce viral shedding, potentially lowering the risk of transmission. However, suppressive therapy with antiviral drugs does not completely eliminate all viral shedding, providing a potential route of transmission for seronegative individuals.

[0009] Despite widespread use of suppressive treatment, HSV infections are exploding, increasing the risk of HIV infection, and the HSV epidemic has become a serious public health risk and pandemic. Current suppressive therapies have significant drawbacks that hinder their effectiveness in reducing HSV transmission from HSV-seropositive to HSV-seronegative individuals. Treatment focused solely on seropositive individuals can create a single point of failure in reducing the likelihood of transmission. For example, if seropositive individuals do not comply with the drug regimen, if the viral strain is resistant to the antiviral agent, and / or if the medication is insufficient, sufficient virus may be transferred to seronegative individuals to create a sustainable infection. This single-target treatment approach relies solely on the effectiveness of a single layer of treatment—the treatment of seropositive subjects—which has failed to adequately reduce HSV epidemics. Furthermore, conventional suppressive therapies generally involve administering a single antiviral drug. This single-drug approach exacerbates the single-point-of-failure problem by failing to realize the cumulative effects of multiple drugs, potentially reducing the likelihood of exposing the virus to optimal drug options. Additionally, as a result of noncompliance, viral strains may evolve and develop resistance to a single drug in use, potentially weakening or even neutralizing this single-layer protection. An even more significant problem is that many people are unaware of their HSV infection or deny their HSV seropositive status, and therefore may be unaware of or not offered suppressive therapy. In a 1997 National Health and Nutrition Examination Survey conducted and published in the New England Journal of Medicine, 91% of people who were seropositive for HSV-2 were unaware of their infection. Furthermore, suppressive therapy offers no protection for HSV-seronegative individuals who may be at risk for HSV exposure other than avoiding direct physical contact with HSV-seropositive individuals. For many individuals, such protection is unavailable, especially in situations where consent or knowledge of other individuals' true serostatus is not established prior to physical activity.The present disclosure addresses the need to provide compositions and methods for preventing HSV infection in seronegative individuals by treating the seronegative individuals with one or more antiviral agents. Additionally, methods and compositions are provided for treating both HSV-seropositive and HSV-seronegative individuals with one or more antiviral agents to further reduce the risk of HSV transmission and infection.

[0010] In one aspect, the present invention provides methods and compositions of matter for preventing and treating human herpesvirus infections. Herpesviruses, in turn, can cause other medical conditions. Thus, the present invention serves to indirectly prevent or alleviate symptoms associated with these other medical conditions.

[0011] In certain embodiments, the present invention provides methods and compositions for preventing and treating diseases representing underlying conditions caused by human herpesvirus infection using combination antiviral therapy, wherein the antiviral drug is valacyclovir, famciclovir, or a similar antiviral drug, and / or a combination thereof. In embodiments, a first antiviral drug is administered in a specific amount in combination with a second antiviral drug or multiple additional antiviral drugs to an individual who is seronegative for one type of herpesvirus. In embodiments, a first antiviral drug is administered in a specific amount in combination with a second antiviral drug or multiple additional antiviral drugs to an individual who is seropositive for herpesvirus but is at risk of infection with the virus.

[0012] In certain embodiments, the use of combinations of antiviral agents can reduce dosing while demonstrating comparable efficacy, potentially reducing toxicity or increasing the overall effectiveness of treatment. Some compounds are individually well tolerated but may exhibit toxic effects when combined (known examples of such non-obvious effects when combined include DDI and DDC, AZT + recombinant alpha-interferon, etc.). As demonstrated herein, it has surprisingly been found that certain combinations of antiviral agents exhibit superior antiviral activity. The present invention fulfills the need for novel combinations of active antiviral drugs against herpes infections that can provide higher levels of efficacy (i.e., reduced viremia, reduced symptom onset, lower infection rates, etc.) while preserving or enhancing the safety profile associated with standard treatment therapies.

[0013] In one aspect, provided herein is a method for preventing HSV infection in an HSV-seronegative subject, the method comprising administering a therapeutically effective amount of a first antiviral agent to the subject prior to physical contact with an HSV-seropositive partner. In some embodiments, the subject is in or plans to be in an ongoing, mutually monogamous sexual relationship with the HSV-seropositive partner. In some embodiments, the subject is not in or plans to be in a mutually monogamous sexual relationship with the HSV-seropositive partner. In some embodiments, the method further comprises administering a therapeutically effective amount of a second antiviral agent to the HSV-seropositive partner. In some embodiments, the method further comprises determining whether the subject is at risk of exposure to HSV prior to administering the first antiviral agent. In some embodiments, the method further comprises determining a therapeutically effective amount of the first antiviral agent. In some embodiments, the administering comprises delivering the first antiviral agent to the subject using a long-acting drug delivery device. In some embodiments, the long-acting drug delivery device is an intravaginal ring.

[0014] In some embodiments, the first antiviral agent comprises valacyclovir, acyclovir, famciclovir, penciclovir, pritelivir, tenofovir, ganciclovir, glycyrrhizinic acid, sambucus nigra, valganciclovir, amenamevir, N-methancocarbathymidine (N-MCT), or a salt, solvate, or combination thereof. In some embodiments, the therapeutically effective amount of the first antiviral agent is about 5 mg to about 10,000 mg. In the case of a combination, the therapeutically effective amount of the second antiviral agent is about 5 mg to about 10,000 mg.

[0015] In some embodiments, the method further comprises administering to the subject a therapeutically effective amount of an additional antiviral agent. In some embodiments, the additional antiviral agent is an HIV antiviral agent. In some embodiments, the HIV antiviral agent comprises tenofovir, emtricitabine, lamivudine, efavirenz, raltegravir, dolutegravir, maravoric, rilpirivine, or a salt, solvate, or combination thereof. In some embodiments, the method further comprises administering to the subject an effective amount of a contraceptive, hi some embodiments, the contraceptive comprises levonorgestrel, estradiol, desogestrel, ethinyl estradiol, norethindrone acetate, norgestimate, or a salt, solvate, or combination thereof.

[0016] In another aspect, provided herein is a method for preventing HSV infection in an HSV-seronegative subject, comprising administering a therapeutically effective amount of a first antiviral agent to the subject after physical contact with a partner who is seropositive for HSV. In some embodiments, the method further comprises administering a therapeutically effective amount of an additional antiviral agent to the subject before physical contact with the HSV-seropositive partner. In some embodiments, the method further comprises administering a therapeutically effective amount of a second antiviral agent to the HSV-seropositive partner. In some embodiments, the method further comprises determining a therapeutically effective amount of the first antiviral agent. In some embodiments, the administering comprises delivering the first antiviral agent to the subject using a long-acting drug delivery device. In some embodiments, the long-acting drug delivery device is an intravaginal ring.

[0017] In some embodiments, the first antiviral agent comprises valacyclovir, acyclovir, famciclovir, penciclovir, pritelivir, tenofovir, ganciclovir, glycyrrhizinic acid, elderberry, valganciclovir, amenamevir, N-methanecocarbathymidine (N-MCT), or a salt, solvate, or combination thereof. In some embodiments, the therapeutically effective amount of the first antiviral agent is from about 500 mg to about 2000 mg. In some embodiments, the method further includes administering to the subject a therapeutically effective amount of an HIV antiviral agent, in some embodiments, the HIV antiviral agent includes tenofovir, emtricitabine, lamivudine, efavirenz, raltegravir, dolutegravir, maravoric, rilpirivine, or a salt, solvate, or combination thereof.

[0018] In some embodiments, the method further comprises administering to the subject an effective amount of a contraceptive. In some embodiments, the contraceptive comprises levonorgestrel, estradiol, desogestrel, ethinyl estradiol, norethindrone acetate, norgestimate, or a salt, solvate, or combination thereof. In some embodiments, the contraceptive is an emergency contraceptive. In some embodiments, the emergency contraceptive comprises levonorgestrel. In another aspect, provided herein is an HSV treatment kit comprising: a) a therapeutically effective amount of a first antiviral agent; b) a delivery device for delivering the first antiviral agent to an HSV-seronegative subject; and c) instructions for use containing information on how to administer the first antiviral agent using the delivery device to prevent HSV infection in the HSV-seronegative subject.

[0019] In some embodiments, the therapeutically effective amount of the first antiviral agent is an amount useful for preventing HSV infection in an HSV-seronegative subject when administered to the HSV-seronegative subject prior to exposure to HSV. In some embodiments, the therapeutically effective amount of the first antiviral agent is an amount useful for suppressing HSV in a seropositive subject, wherein the delivery device further provides a method for delivering the first antiviral agent to an HSV-seropositive subject, and wherein the instructions for use further include information on how to administer the first antiviral agent using the delivery device to suppress HSV reactivation in the HSV-seropositive subject. In some embodiments, the therapeutically effective amount of the first antiviral agent is an amount useful for preventing HSV infection in an HSV-seronegative subject when administered after the HSV-seronegative subject has been exposed to HSV. In some embodiments, the therapeutically effective amount of the first antiviral agent is an amount useful for treating an HSV outbreak in a seropositive subject, wherein the delivery device further provides a method for delivering the first antiviral agent to an HSV-seropositive subject, and wherein the instructions for use further include information on how to administer the first antiviral agent using the delivery device to treat an HSV outbreak in the HSV-seropositive subject. In some embodiments, the delivery device is a long-acting drug delivery device. In some embodiments, the long-acting drug delivery device is an intravaginal ring.

[0020] In some embodiments, the first antiviral agent comprises valacyclovir, acyclovir, famciclovir, penciclovir, pliterivir, tenofovir, ganciclovir, glycyrrhizinic acid, elderberry, valganciclovir, amenamevir, N-methanecocarbathymidine (N-MCT), or a salt, solvate, or combination thereof. In some embodiments, the kit further comprises one or more additional antiviral agents. In some embodiments, the one or more additional antiviral agents comprise an HSV antiviral agent, an HIV antiviral agent, or both an HSV antiviral agent and an HIV antiviral agent. In some embodiments, the HIV antiviral agent comprises tenofovir, emtricitabine, lamivudine, efavirenz, raltegravir, dolutegravir, maravoric, rilpirivine, or a salt, solvate, or combination thereof. In some embodiments, the kit further comprises an effective amount of a contraceptive, hi some embodiments, the contraceptive comprises levonorgestrel, estradiol, desogestrel, ethinyl estradiol, norethindrone acetate, norgestimate, or a salt, solvate, or combination thereof.

[0021] In another aspect, provided herein is a method for preventing HSV infection in an HSV-seronegative subject, comprising administering to the subject a composition comprising a low dose of a first antiviral agent prior to physical contact with an HSV-seropositive partner. In some embodiments, the method comprises administering a low dose of a second antiviral agent prior to physical contact with an HSV-seropositive partner. In some embodiments, the physical contact occurs during a single occasion. In some embodiments, the physical contact occurs during two or more separate occasions. In some embodiments, the physical contact occurs with the HSV-seropositive partner and one or more additional partners. In some embodiments, the physical contact is sexual contact. In some embodiments, the subject and the HSV-seropositive partner use a physical barrier, such as, but not limited to, a male or female condom, during sexual contact. In some embodiments, the subject is in or plans to be in an ongoing, mutually monogamous sexual relationship with the HSV-seropositive partner. In some embodiments, the subject is not in, and does not plan to be in, a mutually monogamous sexual relationship with the HSV-seropositive partner. In some embodiments, the HSV-seropositive partner is aware of their HSV serostatus. In some embodiments, the HSV-seropositive partner is unaware of their HSV serostatus.

[0022] In some embodiments, the HSV-seropositive partner is receiving HSV suppressive therapy, comprising administering a second low dose of a second antiviral agent to the HSV-seropositive partner. In some embodiments, the method further comprises administering a second low dose of a second antiviral agent to the HSV-seropositive partner. In some embodiments, the second antiviral agent comprises the same active agent as the first antiviral agent. In some embodiments, the second antiviral agent comprises a different active agent from the first antiviral agent.

[0023] In some embodiments, the subject is exposed to HSV from an HSV-seropositive partner during physical contact. In some embodiments, the administered composition suppresses HSV replication in the subject. In some embodiments, the administered composition suppresses HSV activation in the subject. In some embodiments, the administered composition reduces the subject's risk of HSV infection. In some embodiments, the subject's risk of HSV infection is reduced by at least about 50%, 60%, 70%, 80%, 90%, or 95%. In some embodiments, the method further includes determining whether the subject is at risk of being exposed to HSV prior to administering the composition. In some embodiments, the subject has been determined to be at risk of being exposed to HSV.

[0024] In some embodiments, the method further comprises determining a dose of the first antiviral agent or the second antiviral agent. In some embodiments, the method further comprises determining a delivery mechanism for administering the composition to the subject. In some embodiments, the delivery mechanism comprises a long-acting drug delivery device. In some embodiments, the long-acting drug delivery device comprises an injection device, an intravaginal ring, a transdermal patch, or a combination thereof. In some embodiments, the dose of the first antiviral agent is from about 5 mg to about 1 g. As non-limiting examples, the composition may comprise about 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10,000 mg of a first antiviral agent.

[0025] In some embodiments, the method comprises determining a dose that provides an effective amount of an antiviral agent according to body mass. As used herein, body mass and body mass are used interchangeably and refer to the mass of a subject, not the force exerted in a gravitational field. In some embodiments, the method comprises determining a dose that provides an effective amount of a second antiviral agent according to body mass. In some embodiments, the method comprises determining the dose of the first and second antiviral agents administered in combination according to body mass. In some embodiments, the dose takes into account the affinity of the antiviral agent for its target. In some embodiments, the dose takes into account the intracellular half-life of the antiviral agent. In some embodiments, the dose takes into account the plasma half-life of the antiviral agent.As non-limiting examples, the compositions may be administered at concentrations of about 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, 100 mg / kg, 110 mg / kg, 125 mg / kg, 130 mg / kg, 140 mg / kg, 150 mg / kg, 160 mg / kg, 175 mg / kg, 180 mg / kg, 190 mg / kg, 210 mg / kg, 220 mg / kg, 230 mg / kg, 240 mg / kg, 250 mg / kg, 260 mg / kg, 270 mg / kg, 280 mg / kg, 290 mg / kg, 300 mg / kg, 310 mg / kg, 320 mg / kg, 330 mg / kg, 340 mg / kg, 350 mg / kg, 360 mg / kg, 370 mg / kg, 380 mg / kg, 390 mg / kg, 400 mg / kg, 410 mg / kg, 420 mg / kg, 430 mg / kg, 440 mg / kg, 450 mg / kg, 460 mg / kg, 470 mg / kg, 480 mg / kg, 490 mg / kg, 50 mg / kg, 60mg / kg, 70mg / kg, 80mg / kg, 90mg / kg, 100mg / kg, 125mg / kg, 150mg / kg, 175mg / kg, 200mg / kg, 225mg / kg, 250mg / kg, 275mg / kg, 300mg / kg, 350mg / kg, 400mg / kg, 500mg / kg, 600mg / kg, 650mg / kg, 700mg / kg, 750mg / kg, 80 0 mg / kg, 850 mg / kg, 900 mg / kg, 950 mg, 1000 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10000 mg, or about 0.5 mg / kg to about 100 mg / kg, or about 0.5 mg / kg to about 10 mg / kg, or about 5 mg / kg to about 50 mg / kg, or about 25 mg / kg to about 250 mg / kg, or about 10 or from about 0 mg / kg to about 250 mg / kg, or from about 100 mg / kg to about 500 mg / kg, or from about 100 mg / kg to about 1000 mg / kg, or from about 125 mg / kg to about 500 mg / kg, or from greater than 100 mg / kg to about 250 mg / kg, or from greater than 100 mg / kg to about 500 mg / kg, or from greater than 100 mg / kg to about 1000 mg / kg of body weight of an antiviral agent.

[0026] Surprisingly, it has been found that certain antiviral agents, when administered in combination, are more effective in treating HSV infection or preventing HSV in subjects. Non-limiting uses include pre-exposure prophylaxis (e.g., preventing infection in seronegative subjects); treatment of early infection (e.g., before or when a seronegative individual is becoming seropositive); prophylaxis in seropositive individuals (preventing recurrent disease); treatment of recurrent infection in seropositive individuals. Furthermore, antiviral agents are useful for the treatment or prophylactic treatment of diseases or conditions associated with HSV infection.

[0027] In certain embodiments, the antiviral agents target the same polymerase. In one exemplary embodiment, the first antiviral agent is valacyclovir and the second antiviral agent is famciclovir. In embodiments involving a combination of a first and a second antiviral agent, the doses of the agents may be the same or different. As a non-limiting example, the composition may be administered at a dose of about 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 ... 0mg / kg, 90mg / kg, 100mg / kg, 125mg / kg, 150mg / kg, 175mg / kg, 200mg / kg, 225mg / kg, 250mg / kg, 275mg / kg, 300mg / kg, 350mg / kg , 400mg / kg, 500mg / kg, 600mg / kg, 650mg / kg, 700mg / kg, 750mg / kg, 800mg / kg, 850mg / kg, 900mg / kg, 950mg / kg, 1000mg / kg, or 2000 mg / kg, or about 0.5 mg / kg to about 1000 mg / kg, or about 0.5 mg / kg to about 100 mg / kg, or about 0.5 mg / kg to about 10 mg / kg, or about 5 mg / kg to about 50 mg / kg, or about 25 mg / kg to about 100 mg / kg, or about 25 mg / kg to about 100 mg / kg, or about 25 mg / kg to about 250 mg / kg, or about 50 mg / kg to about 250 mg / kg, or about 100 mg / kg to about 250 mg / kg kg, or about 100 mg / kg to about 500 mg / kg, or about 100 mg / kg to about 1000 mg / kg, or about 125 mg / kg to about 500 mg / kg, or greater than 100 mg / kg to about 250 mg / kg, or greater than 100 mg / kg to about 500 mg / kg, or greater than 100 mg / kg to about 1000 mg / kg of body weight of a first antiviral agent, as well as about 0.5 mg / kg, 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5mg / kg, 3mg / kg, 4mg / kg, 5mg / kg, 6mg / kg, 7mg / kg, 8mg / kg, 9mg / kg, 10mg / kg, 11mg / kg, 12.5mg / kg, 15mg / kg, 17 .5mg / kg, 20mg / kg, 25mg / kg, 30mg / kg, 40mg / kg, 50mg / kg, 60mg / kg, 70mg / kg, 80mg / kg, 90mg / kg, 100mg / kg, 125 mg / kg, 150mg / kg, 175mg / kg, 200mg / kg, 225mg / kg, 250mg / kg, 275mg / kg, 300mg / kg, 350mg / kg, 400mg / kg, 500mg / kg, 600mg / kg, 650mg / kg, 700mg / kg, 750mg / kg, 800mg / kg, 850mg / kg, 900mg / kg, 950mg, 1000mg, or 2000mg / kg, or about 0.5 mg / kg to about 1000 mg / kg, or about 0.5 mg / kg to about 100 mg / kg, or about 0.5 mg / kg to about 10 mg / kg, or about 5 mg / kg to about 50 mg / kg, or about 25 mg / kg to about 100 mg / kg, or about 25 mg / kg to about 100 mg / kg, or about 25 mg / kg to about 250 mg / kg, or about 50 mg / kg to about 250 mg / kg, or about 100 mg and a second antiviral agent in an amount of from about 100 mg / kg to about 250 mg / kg, or from about 100 mg / kg to about 500 mg / kg, or from about 100 mg / kg to about 1000 mg / kg, or from about 125 mg / kg to about 500 mg / kg, or from greater than 100 mg / kg to about 250 mg / kg, or from greater than 100 mg / kg to about 500 mg / kg, or from greater than 100 mg / kg to about 1000 mg / kg of body weight.

[0028] In certain embodiments, the antiviral agent is administered at a dose ratio of about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, or about 1:5 in mg / kg.

[0029] In certain embodiments, compositions, kits, or devices are provided in which valcyclovir and famciclovir are administered together, hi certain embodiments, valcyclovir and famciclovir are administered to the same subject in need thereof, by the same route or different routes, at the same time or at different times. In certain embodiments, the dose is relatively low, such that when the amount of valcocylovir is about 1 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 1.5 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.In embodiments, when the amount of valcocylovir is about 2 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 2 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 2.5 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.In embodiments, when the amount of valcocylovir is about 3 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 4 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 5 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.In embodiments, when the amount of valcocylovir is about 6 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 7 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 8 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.In embodiments, when the amount of valcocylovir is about 9 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 10 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 11 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.In embodiments, when the amount of valcocylovir is about 12.5 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valacyclovir is about 15 mg / kg, the amount of famciclovir can be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valacyclovir is about 17.5 mg / kg, the amount of famciclovir can be about 1 mg / kg. 1.5mg / kg, 2mg / kg, 2.5mg / kg, 3mg / kg, 4mg / kg, 5mg / kg, 6mg / kg, 7mg / kg, 8mg / kg, 9mg / kg, 10mg / kg, 11mg / kg, 12.5m g / kg, 15mg / kg, 17.5mg / kg, 20mg / kg, 25mg / kg, 30mg / kg, 40mg / kg, 50mg / kg, 60mg / kg, 70mg / kg, 80mg / kg, 90mg / kg, In embodiments, when the amount of valcocylovir is about 20 mg / kg, the amount of famciclovir can be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 25 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 30 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.In embodiments, when the amount of valcocylovir is about 40 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 50 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valacyclovir is about 60 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.In embodiments, when the amount of valcocylovir is about 70 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 80 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg. In embodiments, when the amount of valcocylovir is about 90 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.In embodiments, when the amount of valcocylovir is about 100 mg / kg, the amount of famciclovir may be about 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, or 100 mg / kg.

[0030] In certain embodiments, it may be desirable for the total dose to be less than 1000 mg or less than 2000 mg. For example, in embodiments where the dose ratio of valacyclovir:famciclovir is 2:1, non-limiting dosage amounts include about 500 mg:250 mg, about 600 mg:300 mg, about 650 mg:325 mg, about 700 mg:350 mg, about 800 mg:400 mg, about 900 mg:450 mg, or about 1000 mg:500 mg.

[0031] The absolute dose or weight-based dose tested in animal models may be a human equivalent dose (HED). See, for example, the NIH guidelines and Nair, AB et al., A simple practice guide for dose conversion between animals and humans, J Basic Clin Pharm. March 2016-May 2016; 7(2): 27-31. In the examples shown herein using mice or guinea pigs, the human equivalent dose is used.

[0032] In certain embodiments, one or more antiviral agents used in the combination include an HSV polymerase inhibitor. In certain embodiments, one or more antiviral agents used in the combination include a nucleoside analog. Examples include, but are not limited to, the FDA-approved Famvir (famciclovir), Sitavig (acyclovir), Valtrex (valacyclovir), and Zovirax (acyclovir). In one embodiment, the combination of antiviral agents includes valacyclovir and famciclovir. In another embodiment, the combination of antiviral agents includes acyclovir and penciclovir. In certain embodiments, one or more antiviral agents used in the combination include an HSV helicase-primase inhibitor (HPI). Examples include, but are not limited to, amenamevir and pritelivir. In certain embodiments, the combination includes an HSV polymerase inhibitor and an HSP helicase-primase inhibitor.

[0033] In certain embodiments, the first and second antiviral agents are selected from the group consisting of valacyclovir, acyclovir, famciclovir, penciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, elderberry, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, sarracenia purpurea purpurea), versabase gel containing UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, amenamevir, N-methanecocarbatimidine (N-MCT), or a salt, solvate, or combination thereof.

[0034] Valacyclovir and famciclovir have a similar mechanism of action in that they both target viral DNA. However, these drugs differ in their pharmacokinetic profiles and specificity for viral thymidine kinase. We discovered a surprising and unexpected synergistic effect in the combined action of these drugs. Because both drugs belong to the same class, combining them is not trivial. In fact, increasing the dose of each drug used individually in monotherapy has been shown not to increase the efficacy of the therapy. Because both drugs are nucleoside analogs that target viral DNA, the current recommendation from the CDC and other authorities is to treat herpes infections with either drug, but not to use both drugs in combination therapy.

[0035] Valacyclovir was created by adding a valine moiety to acyclovir, significantly improving its bioavailability and making it a substrate for active transport in the human intestine via the peptide transporters hPEPT-1 and / or HPT-1. Protein binding is minimal (<15%), resulting in good distribution to body tissues, including cerebrospinal fluid (CSF). Acyclovir is primarily phosphorylated by viral thymidine kinase, creating a concentration gradient that increases acyclovir uptake into infected cells. In the absence of viral thymidine kinase, acyclovir remains essentially unchanged and is eliminated by renal tubular secretion and glomerular filtration. This is the primary reason for valacyclovir's excellent safety profile. It is also not metabolized by cytochrome p450, thus limiting drug interactions. Its mechanisms of action are threefold: 1) competitive inhibition of viral DNA polymerase; 2) termination of viral DNA chain elongation; and 3) inactivation of viral DNA polymerase. Its half-life is approximately 2.5 to 3.4 hours. The mean Cmax ranged from 0.83 to 5.65 μg / mL. The mean AUC ranged from 2.27 to 19.62 hours. * The bioavailability of valacyclovir was in the range of 0.2 μg / mL. Renal clearance after a single dose of 1 g was 255 mL / min. Valacyclovir has an overall bioavailability of 54.5% compared to 77% for FCV.

[0036] Compared with valacyclovir, famciclovir has weaker affinity for viral DNA polymerase, a shorter plasma half-life (2–2.5 hours), a longer intracellular half-life (10–20 hours in HSV-infected cells), and higher intracellular concentrations. The time to maximum concentration ranges from 0.5–0.75 hours compared with 1.6–1.9 hours for valacyclovir. Famciclovir also has a high bioavailability of 77%. Because famciclovir does not use the peptide transporters hPEPT-1 or HPT-1, it should be more effective in subjects with deficiencies associated with these transporters.

[0037] The combination of valacyclovir and famciclovir is useful for preventing human herpesvirus infections (i.e., pre-exposure prophylaxis) and for treating and preventing recurrence of herpesvirus symptoms (i.e., post-exposure prophylaxis). The combination is nontoxic at doses that produce potent antiviral activity, is active via the oral route of administration, and is bioavailable.

[0038] Another nucleoside inhibitor of HSV polymerase is N-methanocarbathymidine (N-MCT), which is converted to the active triphosphate metabolite by a three-step phosphorylation process, one of which is selectively accomplished by HSV-TK. N-MCT inhibits HSV-1, HSV-2, and HSV-8 (Kaposi's sarcoma virus), as well as vaccinia and cowpox viruses. It is cytotoxic only in virus-infected cells, active against acyclovir-resistant HSV and cidofovir-resistant cowpox viruses, equally or more potent than the antiviral drugs acyclovir, ganciclovir, and cidofovir, nontoxic at doses that produce potent antiviral activity, orally active, and bioavailable.

[0039] In some embodiments, the first antiviral agent comprises an HSV vaccine and optionally an adjuvant. In some embodiments, the HSV vaccine comprises GSK208141 (gD2t, GSK glycoprotein D (gD)-Alum / 3-deacylated form of monophosphoryl lipid A), varicella-zoster GSK1437173A, gD2-ASO4, Havrix®, gD-Alum, Zostavax / varicella-zoster vaccine (V211, V212, V210), HSV529, HerpV (AG-707 rh-Hsc70 multivalent peptide complex), VCL-HB01, VCL-HM01, pPJV7630, GEN-003, SPL7013 gel (VivaGel®), GSK324332A, or a salt, solvate, or combination thereof.

[0040] In some embodiments, the composition further comprises an additional antiviral agent. In some embodiments, the method further comprises administering to the subject an additional antiviral agent. In some embodiments, the additional antiviral agent is administered to a subject at a dose of about 50 mg to about 1 g, e.g., about 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10000 mg. In some embodiments, the additional antiviral agent is an HIV antiviral agent.In some embodiments, the HIV antiviral agent is abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasvir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine, nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, TMC125, adefovir, dapivirine, lersivirine, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir, droxinavir, Emtriva, invivivir enzyme, agenerase, maraviroc, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibody, DCM205, DARPins, caprin antibody, VIR-576, enfuvirtide, AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsen, lectin, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, or a salt, solvate, or combination thereof.

[0041] In some embodiments, the composition further comprises a contraceptive. In some embodiments, the method further comprises administering to the subject an effective dose of a contraceptive. In some embodiments, the contraceptive is selected from the group consisting of ethinyl estradiol, norethindrone, desogestrel, levonorgestrel, ethynodiol diacetate, ethynodiol diacetate, RU486, N9, mifepristone, mifegin, mifeprex, 17a-ethynyl-levonorgestrel, 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, medroxyprogesterone acetate, nestrone, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, norgestimate, megestrol, etono-progestin, alonegestrel, etono-progestin, alonegestrel), 17-acetoxy-16-methylene-19-norprogesterone, or a salt, solvate, or combination thereof.

[0042] In another aspect, provided herein is an HSV treatment kit comprising: a) a composition comprising a dose of a first antiviral agent, or a dose of a first antiviral agent and a dose of a second antiviral agent; b) a delivery device for delivering the composition to an HSV-seronegative subject; and c) instructions for use, the instructions comprising information on how to administer the composition using the delivery device to prevent HSV infection in an HSV-seronegative subject. In some embodiments, HSV prevention comprises suppressing HSV replication in an HSV-seronegative subject. In some embodiments, HSV prevention comprises suppressing HSV activation in an HSV-seronegative subject.

[0043] In some embodiments, the dose of the first antiviral agent is an amount useful for both preventing HSV infection in an HSV-seronegative subject and suppressing HSV in a seropositive subject. As non-limiting examples, the dose is about 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10000 mg of the first antiviral agent. When a second antiviral agent is present, by way of non-limiting example, the dose of the second agent is about 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10000 mg. In some embodiments, the delivery device further provides a method for delivering the composition to an HSV-seropositive subject. In some embodiments, the instructions further include information on how to administer the composition using the delivery device to inhibit HSV reactivation in an HSV-seropositive subject.

[0044] In some embodiments, the kit further comprises or is enclosed within packaging, hi some embodiments, the packaging comprises labeling directed to HSV-seronegative subjects, HSV-seropositive subjects, and subjects of unknown HSV serostatus. In some embodiments, the delivery device comprises an oral tablet, an oral capsule, or an oral liquid. In some embodiments, the delivery device is a long-acting drug delivery device. In some embodiments, the long-acting delivery device comprises an injection device, an intravaginal ring, a transdermal patch, or a combination thereof. In some embodiments, delivery devices, including, but not limited to, ingested tablets, capsules, or liquids, provide systemic delivery.

[0045] In some embodiments, the first antiviral agent is valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, elderberry, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, amenamevir, N-methanecocarbatimidine (N-MCT), or a salt, solvate, or combination thereof.

[0046] In some embodiments, the dose of the first antiviral agent is about 5 mg to about 1 g or higher, e.g., about 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10000 mg.

[0047] In some embodiments, the kit further comprises a second antiviral agent, hi some embodiments, the second antiviral agent is present in the composition at a second dose. In some embodiments, the second lower dose is about 5 mg to about 1 g, e.g., about 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 2000 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10000 mg. In some embodiments, the second antiviral agent is an HSV antiviral agent. In some embodiments, the second antiviral agent is an HIV antiviral agent.In some embodiments, the HIV antiviral agent is abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasvir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine, nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, TMC125, adefovir, dapivirine, lersivirine, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir, droxinavir, Emtriva, Invirase, age including nerase, maraviroc, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibodies, DCM205, DARPins, caprin antibodies, VIR-576, enfuvirtide, AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsen, lectin, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, or a salt, solvate, or combination thereof.

[0048] In some embodiments, the kit further comprises a contraceptive. In some embodiments, the contraceptive comprises ethinyl estradiol, norethindrone, desogestrel, levonorgestrel, ethynodiol diacetate, ethynodiol diacetate, RU486, N9, mifepristone, mifegine, mifeprex, 17a-ethynyl-levonorgestrel, 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, medroxyprogesterone acetate, nestrone, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, norgestimate, megestrol, etono-progestin alonegestrel, 17-acetoxy-16-methylene-19-norprogesterone, or a salt, solvate, or combination thereof.

[0049] In another aspect, provided herein is a method for preventing HSV infection in an HSV-seronegative subject, comprising administering to the subject a composition comprising a very high dose of a first antiviral agent after physical contact with an HSV-seropositive partner. In some embodiments, the method further comprises administering to the subject a low dose of a second antiviral agent before physical contact with the HSV-seropositive partner. In some embodiments, the second antiviral agent comprises the same active agent as the first antiviral agent. In some embodiments, the second antiviral agent comprises a different active agent from the first antiviral agent. In some embodiments, the physical contact occurs during a single occasion. In some embodiments, the physical contact occurs during two or more separate occasions.

[0050] In some embodiments, the physical contact occurs between the HSV-seropositive partner and one or more additional partners. In some embodiments, the subject is in or plans to be in an ongoing, mutually monogamous sexual relationship with the HSV-seropositive partner. In some embodiments, the subject is not in or plans to be in a mutually monogamous sexual relationship with the HSV-seropositive partner. In some embodiments, the HSV-seropositive partner is aware of his or her HSV serostatus. In some embodiments, the HSV-seropositive partner is unaware of his or her HSV serostatus. In some embodiments, the HSV-seropositive partner is undergoing HSV suppressive therapy, comprising administering a suppressive antiviral agent to the HSV-seropositive partner. In some embodiments, the method further comprises administering a suppressive antiviral agent to the HSV-seropositive partner. In some embodiments, the suppressive antiviral agent comprises the same active agent as the first antiviral agent. In some embodiments, the suppressive antiviral agent comprises a different active agent from the first antiviral agent. In some embodiments, the physical contact is sexual contact. In some embodiments, the subject and the HSV-seropositive partner use a physical barrier during sexual contact. In some embodiments, the physical contact is kissing.

[0051] In some embodiments, the subject is exposed to HSV from an HSV-seropositive partner during physical contact. In some embodiments, the administered composition suppresses HSV replication in the subject. In some embodiments, the administered composition suppresses HSV activation in the subject. In some embodiments, the administered composition reduces the subject's risk of HSV infection. In some embodiments, the subject's risk of HSV infection is reduced by at least about 50%, 60%, 70%, 80%, 90%, or 95%. In some embodiments, the method further comprises determining a very high dose of the first antiviral agent. In some embodiments, the method further comprises determining a delivery mechanism for administering the composition to the subject. In some embodiments, the delivery mechanism comprises a long-acting drug delivery device. In some embodiments, the long-acting drug delivery device comprises an injection device, an intravaginal ring, a transdermal patch, or a combination thereof.

[0052] In some embodiments, the first antiviral agent is valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, elderberry, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, amenamevir, N-methanecocarbatimidine (N-MCT), or a salt, solvate, or combination thereof.

[0053] In some embodiments, the first antiviral agent comprises an HSV vaccine and optionally an adjuvant. In some embodiments, the HSV vaccine comprises GSK208141 (gD2t, GSK glycoprotein D (gD)-Alum / 3-deacylated form of monophosphoryl lipid A), varicella-zoster GSK1437173A, gD2-ASO4, Havrix®, gD-Alum, Zostavax / varicella-zoster vaccine (V211, V212, V210), HSV529, HerpV (AG-707 rh-Hsc70 multivalent peptide complex), VCL-HB01, VCL-HM01, pPJV7630, GEN-003, SPL7013 gel (VivaGel®), GSK324332A, or a salt, solvate, or combination thereof.

[0054] In some embodiments, the very high dose of the first antiviral agent is about 500 mg to about 10,000 mg, e.g., about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, or 2500 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10,000 mg. In some embodiments, the very high dose of the first antiviral agent is greater than the amount useful for treating an early outbreak of HSV in a seropositive patient. In some embodiments, the composition further comprises an additional antiviral agent. In some embodiments, the method further comprises administering the additional antiviral agent to the subject. In some embodiments, the additional antiviral agent is administered to the subject at a dosage of about 500 mg to about 10,000 mg, e.g., 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, 2500 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10000 mg. Doses up to 1000 mg are referred to as "low doses." In some embodiments, the additional antiviral agent is an HIV antiviral agent.In some embodiments, the HIV antiviral agent is abacavir, didanosine, emtrictabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate. fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasvir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine, nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, TMC125, adefovir, dapivirine, lersivirine, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir, droxinavir, Emtriva, Invirase, age including nerase, maraviroc, enfuvirtide, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibodies, DCM205, DARPins, caprin antibodies, VIR-576, AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsen, lectin, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, or a salt, solvate, or combination thereof.

[0055] In some embodiments, the composition further comprises a contraceptive. In some embodiments, the method further comprises administering to the subject an effective dose of a contraceptive. In some embodiments, the contraceptive comprises ethinyl estradiol, norethindrone, desogestrel, levonorgestrel, ethynodiol diacetate, ethynodiol diacetate, RU486, N9, mifepristone, mifegine, mifeprex, 17a-ethynyl-levonorgestrel, 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, medroxyprogesterone acetate, nestrone, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, norgestimate, megestrol, etono-progestin alonegestrel, 17-acetoxy-16-methylene-19-norprogesterone, or a salt, solvate, or combination thereof. In some embodiments, the contraceptive is an emergency contraceptive.

[0056] In another aspect, provided herein is an HSV treatment kit comprising: a) a composition comprising a very high dose of a first antiviral agent; b) a delivery device for delivering the composition to an HSV-seronegative subject; and c) instructions for use, the instructions including information on how to administer the composition using the delivery device to prevent HSV infection in an HSV-seronegative subject after the HSV-seronegative subject has been exposed to HSV. In some embodiments, HSV prevention comprises suppressing HSV replication in the HSV-seronegative subject. In some embodiments, HSV prevention comprises suppressing HSV activation in the HSV-seronegative subject.

[0057] In some embodiments, the very high dose of the first antiviral agent is an amount that is useful for both preventing HSV infection in HSV-seronegative subjects after exposure to HSV and treating early outbreaks of HSV in seropositive subjects. In some embodiments, the very high dose of the first antiviral agent is an amount that is greater than the amount that is useful for treating early outbreaks of HSV in seropositive patients.

[0058] In some embodiments, the delivery device further provides a method for delivering the composition to an HSV-seropositive subject. In some embodiments, the instructions further include information on how to administer the composition using the delivery device to treat an HSV outbreak in an HSV-seropositive subject. In some embodiments, the kit further comprises or is enclosed within packaging, hi some embodiments, the packaging comprises labeling directed to HSV-seronegative subjects, HSV-seropositive subjects, and subjects of unknown HSV serostatus.

[0059] In some embodiments, the delivery device comprises an oral tablet, an oral capsule, or an oral liquid. In some embodiments, the delivery device is a long-acting drug delivery device. In some embodiments, the long-acting delivery device comprises an injection device, an intravaginal ring, a transdermal patch, or a combination thereof. In some embodiments, the first antiviral agent is valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, elderberry, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or a salt, solvate, or combination thereof.

[0060] In some embodiments, the very high dose of the first antiviral agent is about 500 mg to about 2500 mg, e.g., about 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, 2500 mg, 3000 mg, 4000 mg, 5000 mg, 6000 mg, 8000 mg, or 10000 mg.

[0061] In some embodiments, the kit further comprises a second antiviral agent. In some embodiments, the second antiviral agent is an HSV antiviral agent. In some embodiments, the second antiviral agent is an HIV antiviral agent. In some embodiments, the HIV antiviral agent is abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate, or the like. fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasvir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine, nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, TMC125, adefovir, dapivirine, lersibiric acid Lin, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir, droxinavir, emtriva, invirase, agenerase, maraviroc, enfuvirtide, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO 140, b12 antibody, DCM205, DARPins, caprin antibody, VIR-576, AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsen, lectin, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, or a salt, solvate, or combination thereof.

[0062] In some embodiments, the kit further comprises a contraceptive. In some embodiments, the contraceptive comprises ethinyl estradiol, norethindrone, desogestrel, levonorgestrel, ethynodiol diacetate, ethynodiol diacetate, RU486, N9, mifepristone, mifegine, mifeprex, 17a-ethynyl-levonorgestrel, 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, medroxyprogesterone acetate, nestrone, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, norgestimate, megestrol, etono-progestin alonegestrel, 17-acetoxy-16-methylene-19-norprogesterone, or a salt, solvate, or combination thereof. In some embodiments, the kit comprises an emergency contraceptive. The following detailed description, given by way of example and not intended to limit the invention to only the specific embodiments described, can be best understood in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0063] [Figure 1] Figure 1 shows the experimental design. Days -7 and -1: Mice are weighed and treated with medroxyprogesterone; Day -7: Mice are dosed daily; Day 0: Mice are infected intravaginally with 105 HSV-2 MS; Days 1-28: Mice are treated daily, weighed, clinically scored, and mice meeting IACUC human endpoint guidelines are euthanized; Days 7, 14, 21, and 28: Vaginal swabs are collected; Day 28: End of study, DRGs are collected. [Figure 2]Figures 2A-2G show survival curves. Mice in Group 9 were treated with 125 mg / kg valacyclovir and 63 mg / kg famciclovir and mock-infected. Mice in Group 10 were mock-treated and mock-infected. Mice were monitored daily for survival. Comparison of survival curves was performed by log-rank (Mantel-Cox) test. ***p<0.001. (A) Mice in Group 1 were treated daily with 125 mg / kg valacyclovir by oral gavage beginning 7 days prior to infection. Groups 1 and 8 (mock-treated) were infected intravaginally with 105 HSV-2 MS strain. (B) Mice in Group 2 were treated daily with 63 mg / kg famciclovir by oral gavage beginning 7 days prior to infection. Groups 2 and 8 (mock-treated) were infected intravaginally with 105 HSV-2 MS strain. (C) Mice in group 3 were treated daily with 32 mg / kg valacyclovir and 16 mg / kg famciclovir by oral gavage beginning 7 days before infection. Groups 3 and 8 (mock-treated) were infected intravaginally with 105 HSV-2 MS strain. (D) Mice in group 4 were treated daily with 63 mg / kg valacyclovir and 32 mg / kg famciclovir by oral gavage beginning 7 days before infection. Groups 4 and 8 (mock-treated) were infected intravaginally with 105 HSV-2 MS strain. (E) Mice in group 5 were treated daily with 125 mg / kg valacyclovir and 63 mg / kg famciclovir by oral gavage beginning 7 days before infection. Groups 5 and 8 (mock-treated) were infected intravaginally with 105 HSV-2 MS strain. (F) Mice in group 6 were treated daily with 250 mg / kg valacyclovir and 125 mg / kg famciclovir by oral gavage beginning 7 days before infection. Groups 6 and 8 (mock-treated) were infected intravaginally with 105 HSV-2 MS strain. (G) Mice in group 7 were treated daily with 500 mg / kg valacyclovir and 250 mg / kg famciclovir by oral gavage beginning 7 days before infection. Groups 7 and 8 (mock-treated) were infected intravaginally with 105 HSV-2 MS strain. [Figure 3]Figure 3 shows the survival curves of compound-treated HSV-2 infected mice. Mice in groups 1-7 were treated daily by oral gavage with various doses and combinations of the drugs valacyclovir and famciclovir (Table 1) beginning 7 days before infection. Mice were monitored daily for survival. [Figure 4] Figures 4A-4H show post-infection body weights as a percentage of original body weight. Comparisons are made to control HSV-2-infected mice in Group 8, control compound-treated mice in Group 9, and control mock-infected and mock-treated mice in Group 10. Mice were weighed daily during infection, and the percentage of original body weight was calculated. (A) Mice in Group 1 were treated daily with 125 mg / kg valacyclovir by oral gavage beginning 7 days prior to infection. (B) Mice in Group 2 were treated daily with 63 mg / kg famciclovir by oral gavage beginning 7 days prior to infection. (C) Mice in Group 3 were treated daily with 32 mg / kg valacyclovir or 16 mg / kg famciclovir by oral gavage beginning 7 days prior to infection. (D) Mice in Group 4 were treated daily with 63 mg / kg valacyclovir or 32 mg / kg famciclovir by oral gavage beginning 7 days prior to infection. (E) Mice in group 4 were treated daily with 63 mg / kg valacyclovir and 32 mg / kg famciclovir by oral gavage beginning 7 days before infection. (F) Mice in group 5 were treated daily with 125 mg / kg valacyclovir and 63 mg / kg famciclovir by oral gavage beginning 7 days before infection. (G) Mice in group 6 were treated daily with 250 mg / kg valacyclovir and 125 mg / kg famciclovir by oral gavage beginning 7 days before infection. (H) Mice in group 7 were treated daily with 500 mg / kg valacyclovir and 250 mg / kg famciclovir by oral gavage beginning 7 days before infection. [Figure 5]Figures 5A-5D show the clinical scores for groups 1-4. Mice were monitored daily post-infection for vaginal clinical scores using a 4-point system (Table 4): 0 = no disease, 1 + redness or swelling (genital erythema), 2 + several small vesicles (moderate genital infection), 3 + purulent genital ulcers, hair loss, poor condition, and 4 + severe ulcers with maceration and hind limb paralysis (leading to euthanasia). (A) Group 1 compared to control. (B) Group 2 compared to control. (C) Group 3 compared to control. (D) Group 4 compared to control. [Figure 6] Figures 6A-6C show the clinical scores for groups 5-7. Mice were monitored daily post-infection for vaginal clinical scores using a 4-point system (Table 4): 0 = no disease, 1 + redness or swelling (genital erythema), 2 + several small vesicles (moderate genital infection), 3 + purulent genital ulcers, hair loss, poor condition, and 4 + severe ulcers with maceration and hind limb paralysis (leading to euthanasia). (A) Group 5 compared to control. (B) Group 6 compared to control. (C) Group 7 compared to control. [Figure 7] Figure 7 shows a comparison of clinical scores in treated mice. Mice were treated with various doses of compound and infected with HSV-2. Mice were monitored daily post-infection for vaginal clinical scores using a 4-point system (Table 4): 0 = no disease, 1 + redness or swelling (genital erythema), 2 + several small vesicles (moderate genital infection), 3 + purulent genital ulcers, hair loss, poor condition, and 4 + severe ulcers with maceration and hind limb paralysis (leading to euthanasia). Comparison of group clinical scores in HSV-2-infected, compound-treated mice. The clinical score for Group 3 was significantly higher than all other groups of infected and treated mice (2-way ANOVA, p < 0.0001). [Figure 8]Figure 8 shows hair loss after infection with HSV-2. Mice were treated with various doses of compound and infected with HSV-2. Mice were monitored daily post-infection for hair loss using the following point system (Table 5): 0.5 mild hair loss, 1+ patches of hair loss, 2+ widespread hair loss on the back, 3+ widespread hair loss on the back and extremities. Comparison of hair loss scores between groups in HSV-2 infected, compound-treated mice. [Figure 9] Figures 9A-9D show disease scores after infection with HSV-2. Mice were treated with various doses of compound and infected with HSV-2. Disease scores were recorded daily using a 4-point system (Table 6): 0 = healthy, 1 + ruffled fur, 2 + arched back, 3 + lethargic to palpation, and 4 + paralysis of one or both hind legs. (A) Group 1 compared to control. (B) Group 2 compared to control. (C) Group 3 compared to control. (D) Group 4 compared to control. Note that after 7 days, only 3 / 15 mice in Group 8 (untreated / infected) survived. [Figure 10] 10A-10C show disease scores after infection with HSV-2. Mice were treated with various doses of compounds and infected with HSV-2. Disease scores were recorded daily using a 4-point system (Table 6): 0 = healthy, 1 + ruffled fur, 2 + arched back, 3 + lethargic to palpation, and 4 + paralysis of one or both hind legs. (A) Group 5 compared to control. (B) Group 6 compared to control. (C) Group 7 compared to control. [Figure 11] Figure 11 shows post-infection body weights as % of original body weight for groups 1 and 2 compared to 5. Mice in group 1 were treated daily with 125 mg / kg valacyclovir. Mice in group 2 were treated daily with 63 mg / kg famciclovir. Mice in group 5 were treated daily with 125 mg / kg valacyclovir and 63 mg / kg famciclovir. All drugs were administered by oral gavage starting 7 days before HSV-2 infection. Mice were weighed daily during infection and the % of original body weight was calculated. [Figure 12]Figure 12 shows the disease scores for groups 1, 2, and 5 after infection with HSV-2. Mice were treated with various doses of compound and infected with HSV-2. Disease scores were recorded daily using a 4-point system (Table 6): 0 = healthy, 1 + ruffled fur, 2 + arched back, 3 + lethargic to palpation, and 4 + paralysis of one or both hind legs. [Figure 13] Figure 13 shows clinical scores, groups 1, 2 and 5. Mice were monitored daily post-infection for vaginal clinical scores using a 4-point system (Table 2): 0 = no disease, 1 + redness or swelling (genital erythema), 2 + several small vesicles (moderate genital infection), 3 + purulent genital ulcers, hair loss, poor condition and 4 + severe ulcers with maceration, hind limb paralysis (leading to euthanasia). [Figure 14] 14A-14B show EC50 and EC90 determinations. (A) EC50 and EC90 clinical score calculations. Mice treated with a 2-fold dose combination of drugs A and B were analyzed compared to mock-treated controls (0). The EC50 was calculated to be 4.898, and the EC90 was 5.98-fold drug-free. Black dots indicate the clinical score of group 2, compound B alone at a 6-fold drug dose, and green dots indicate the clinical index of group 1, treated with compound A alone at a 6-fold drug dose. (B) EC50 and EC90 survival calculations. Mice treated with a 2-fold dose combination of drugs A and B were analyzed compared to mock-treated controls (0). The EC50 was calculated to be 0.7689, and the EC90 was 2.3-fold drug-free. [Figure 15]Figures 15A-15B show clinical score dose response. (A) Combination of drugs A and B. Mice treated with a 2-fold dose combination of drugs A and B were analyzed compared to mock-treated controls (0). The area under the curve for clinical scores for each group was calculated and then plotted. Black dots indicate the clinical score for group 2, treated with only compound B at a 6-fold drug dose, while green dots indicate the clinical index for group 1, treated with only compound A at a 6-fold drug dose. The correlation between clinical score and drug dose was significant, p=0.0215. (B) Single drugs compared to drug combinations. Mice were treated with either B, famciclovir, or A, valacyclovir, or both A and B. The area under the curve for clinical scores for each group was calculated and then plotted. [Figure 16] Figure 16 shows the area under the curve (AUC) of disease scores after infection. Mice treated with two-fold dose combinations of drugs A and B were analyzed compared to mock-treated controls (0). The area under the curve of clinical scores for each group was calculated and then plotted. The TD50 (toxic dose) was calculated to be 8.113. [Figure 17] 17 is a diagram showing the copy number of HSV DNA. The copy number of HSV virus / reaction of groups 1 to 10. The lower limit of detection is 3 molecules. [Figure 18] Figure 18 shows HSV DNA copy number. HSV viral copy number / μg DNA in mock, treated, and untreated infected animals. [Figure 19] Figure 19 shows plasma concentrations of VACV equivalents in female BALB / c mice. Animals were administered VACV by the iv (Group 1; 125 mg / kg) and po (Groups 2, 4-8; 32-500 mg / kg) routes. The amount of VACV equivalents represents the sum of VLAC and the metabolite, ACV. [Figure 20] Figure 20 shows plasma concentrations of FCV equivalents in female BALB / c mice. Animals were administered FCV by the iv (Group 1; 63 mg / kg) and po (Groups 3-8; 16-250 mg / kg) routes. [Figure 21]Figure 21 shows plasma concentrations of PCV in female BALB / c mice. Animals were administered FCV by the iv (Group 1; 63 mg / kg) and po (Groups 3-8; 16-250 mg / kg) routes. PCV, a metabolite of FCV, was measured in plasma. [Figure 22] Figure 22 shows the AUC values ​​of VACV equivalents, representing the concentrations of both VACV and its metabolite ACV in female BALB / c mice. The dose of VACV administered to mice in each group is shown on the graph. Group 1, VACV, 125 mg / kg, was co-administered with FCV via the iv route. Group 2 received VACV alone via the po route. Groups 4-8 received a combination of VACV and FCV via the po route. [Figure 23] Figure 23 shows the AUC values ​​of FCV equivalents in female BALB / c mice. The dose of FCV administered to mice in each group is shown on the graph. For Group 1, FCV, 63 mg / kg, was co-administered with VACV by the iv route. Group 3 received FCV alone by the po route. Groups 4-8 received a combination of VACV and FCV by the po route. [Figure 24] Figure 24 shows the AUC values ​​of PCV, a metabolite of FCV, in female BALB / c mice. The dose of FCV administered to mice in each group is shown on the graph. For Group 1, FCV, 63 mg / kg, was co-administered with VACV via the iv route. For Group 3, FCV alone was administered via the po route. For Groups 4 to 8, a combination of VACV and FCV was administered via the po route. [Figure 25]25A-25C show representative plasma standard curves for the analysis of acyclovir (A), famciclovir (B), and penciclovir (C). (A) Acyclovir: Coefficient of determination: R = 0.993363; Calibration curve cure):-2.34606e-010*x2+2.88714e-005*x+0.000510796;Response type: Internal standard 1mg / kg, 1.5mg / kg, 2mg / kg, 2.5mg / kg, 3mg / kg, 4mg / kg, 5mg / kg, 6mg / kg, 7mg / kg, 8mg / k g, 9mg / kg, 10mg / kg, 11mg / kg, 12.5mg / kg, 15mg / kg, 17.5mg / kg, 20mg / kg, 25mg / kg, 30mg / kg, 40mg / kg, 50mg / kg, 60mg / kg, 70mg / kg, 80mg / kg, 90mg / kg, 100mg / kg , 125mg / kg, 150mg / kg, 175mg / kg, 200mg / kg, 225mg / kg, 250mg / kg, 275mg / kg, 300mg / kg, 350mg / kg, 400mg / kg, 500mg / kg, 600mg / kg, 650mg / kg, 700mg / kg, 750mg / kg, 800mg / kg, 850mg / kg, 900mg / kg, 950mg, 1000mg, 2000mg, 3000mg, 4000mg, 5000mg, 6000mg, 8000mg, Area*(IS concentration / IS area); Curve type: quadratic; Origin: not included; Weighting: 1 / y; Axis transformation: none.(B) Famciclovir esterase product: Coefficient of determination: R2 = 0.982788; Calibration curve: 1.69416e-008*x2 + 0.00017409*x + - 0.000628661; Response type: Internal standard 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, 100 mg / kg, 125mg / kg, 150mg / kg, 175mg / kg, 200mg / kg, 225mg / kg, 250mg / kg, 275mg / kg, 300mg / kg, 350mg / kg, 400mg / kg, 500mg / kg, 600mg / kg, 650mg / kg, 700mg / kg, 750mg / kg, 800mg / kg, 850mg / kg, 900mg / kg, 950mg, 1000mg, 2000mg, 3000mg, 4000mg, 5000mg, 6000mg, 8000mg; Area*(IS concentration / IS area); Curve type: quadratic; Origin: not included; Weighting: 1 / y; Axis transformation: none.(C) Penciclovir: Coefficient of determination: R2 = 0.983086; Calibration curve: 3.428e-011*x2 + 1.4895e-005*x + 0.000210822; Response type: Internal standard 1 mg / kg, 1.5 mg / kg, 2 mg / kg, 2.5 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12.5 mg / kg, 15 mg / kg, 17.5 mg / kg, 20 mg / kg, 25 mg / kg, 30 mg / kg, 40 mg / kg, 50 mg / kg, 60 mg / kg, 70 mg / kg, 80 mg / kg, 90 mg / kg, 100 mg / kg, 1 25mg / kg, 150mg / kg, 175mg / kg, 200mg / kg, 225mg / kg, 250mg / kg, 275mg / kg, 300mg / kg, 350mg / kg, 400mg / kg, 500mg / kg, 600mg / kg, 650mg / kg, 700mg / kg, 750mg / kg, 800mg / kg, 850mg / kg, 900mg / kg, 950mg, 1000mg, 2000mg, 3000mg, 4000mg, 5000mg, 6000mg, 8000mg, Area*(IS Concentration / IS Area); Curve Type: Quadratic; Origin: Not Included; Weighting: 1 / y; Axis Transformation: None. DETAILED DESCRIPTION OF THE INVENTION

[0064] The drawings herein are for illustrative purposes only and are not necessarily drawn to scale.

[0065] The current standard practice for preventing HSV infection involves suppressively treating HSV-seropositive individuals to reduce transmission of the virus to HSV-seronegative individuals. As previously explained, these methods rely on compliance from the HSV-seropositive individual and often do not provide adequate protection to the HSV-seronegative individual. In various embodiments, described herein are methods for preventing HSV infection in a seronegative individual, comprising administering to the seronegative individual a composition comprising one or more antiviral agents. When the HSV-seronegative individual is in a relationship with an HSV-seropositive partner (i.e., an HSV-mismatched relationship), the method may further comprise suppressively treating the HSV-seropositive individual, providing a second layer of protection for the seronegative individual. In one embodiment, compositions comprising one or more antiviral agents useful for preventing HSV infection in an HSV-seronegative individual are provided, which protect the seronegative individual from transmission of shed virus from the seropositive individual. Such antiviral compositions for protecting HSV-seronegative individuals may also be useful for suppressively treating HSV-seropositive individuals. In some aspects of the methods described herein, the HSV composition further comprises and / or is administered in conjunction with one or more additional antiviral agents. For example, the compositions described herein comprise one or more HSV antiviral agents and one or more human immunodeficiency virus (HIV) antiviral agents. In some cases, the HSV antiviral agents also treat or prevent infection by another virus, such as HIV. In additional embodiments, the composition comprising an HSV antiviral agent and optionally one or more additional antiviral agents further comprises and / or is administered in conjunction with a contraceptive agent. Thus, in various embodiments, the present disclosure provides compositions and methods for preventing HSV infection in HSV-seronegative individuals, which may further prevent pregnancy and / or infection by additional viruses.

[0066] In one aspect of the present disclosure, the present specification describes compositions and methods for preventing HSV infection in HSV-seronegative individuals at risk of exposure to HSV.In some cases, these compositions are referred to as pre-exposure compositions or HSV pre-exposure compositions.In some embodiments, HSV-seronegative individuals are at risk of exposure to HSV through one or more sexual contact events with one or more partners, and one or more partners are HSV-seropositive or have unknown HSV serostatus.As an example, HSV-seronegative individuals at risk of exposure to HSV are likely to engage in one or more sexual contact events with the same partner.In some cases, the seronegative individuals and their partners are in a monogamous relationship.In other cases, the seronegative individuals and their partners are not in a monogamous relationship.As another example, HSV-seronegative individuals at risk of exposure to HSV are likely to engage in one or more sexual contact events with one or more different partners. In various embodiments, the pre-exposure compositions described herein comprise a low dose of one or more antiviral agents, e.g., a dose that is the same as or 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% less than the dose typically administered to an HSV-seropositive individual for suppressive therapy.

[0067] In another aspect, the present specification describes compositions and methods for preventing HSV infection in HSV-seronegative individuals after exposure to HSV. In some cases, these compositions are referred to as post-exposure compositions or HSV post-exposure compositions. In some embodiments, the HSV-seronegative individual has been exposed to HSV through one or more sexual contact events with one or more partners, and the one or more partners are HSV-seropositive. In some cases, the HSV-seropositive partner is aware of its seropositive status. In other cases, the HSV-seropositive partner is unaware of its seropositive status. As an example, the HSV-seronegative individual has been exposed to HSV through one or more sexual contact events with the same HSV-seropositive partner. In some cases, the seronegative individual and the partner are in a monogamous relationship. In other cases, the seronegative individual and the partner are not in a monogamous relationship. As another example, the HSV-seronegative individual has been exposed to HSV through one or more sexual contact events with one or more different partners. In various embodiments, the post-exposure compositions described herein comprise a high dose of one or more antiviral agents, e.g., the same as or 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% greater than the dose typically administered to HSV-seropositive individuals for therapy after an initial outbreak.

[0068] In some embodiments, the HSV composition or antiviral composition refers to a pre-exposure composition. In some embodiments, the HSV composition or antiviral composition refers to a post-exposure composition. In some embodiments, the HSV composition or antiviral composition refers to a composition comprising one or more antiviral agents for suppressive therapy of HSV-seropositive individuals. In some embodiments, the HSV composition or antiviral composition refers to both a pre-exposure composition and a post-exposure composition. In further embodiments, the HSV composition or antiviral composition refers to a pre-exposure composition, a post-exposure composition, and a composition for suppressive therapy.

[0069] In one aspect of the present disclosure, compositions and methods are provided herein for preventing HSV infection in an HSV-seronegative subject who is HSV-discordant with an HSV-seropositive subject. In some embodiments, the HSV-seronegative subject is administered a first composition comprising one or more first antiviral agents, and the HSV-seropositive subject is administered a second composition comprising one or more second antiviral agents. In some cases, the first antiviral agent, or a pharmaceutically acceptable salt or solvate thereof, contains the same active agent as the second antiviral agent, or a pharmaceutically acceptable salt or solvate thereof. In some cases, the first antiviral agent contains a different active agent from the second antiviral agent. In some cases, the first antiviral agent is administered in the same or a different dosage than the second antiviral agent. In some cases, the first composition is delivered using the same delivery mechanism as the second composition. In other cases, the first composition is delivered using a different delivery mechanism than the second composition. In some cases, such methods further provide enhanced protection against HSV infection in seronegative individuals by, for example, improving delivery of antiviral agents to seropositive and / or seronegative individuals by using long-acting drug delivery mechanisms. In some embodiments, the composition administered to an HSV-seronegative individual is a pre-exposure composition for prophylactic treatment. In some embodiments, the composition administered to an HSV-seronegative individual is a post-exposure composition for prophylactic treatment. When used in conjunction with suppressive treatment of an HSV-seropositive individual, prophylactic treatment of an HSV-seronegative individual provides a second opportunity to inactivate any virus shed by the seropositive individual so that there is not enough HSV present to create a productive, sustainable infection in a new host, thus creating an additional layer of protection against HSV infection. In some embodiments, this enhanced protection against HSV infection is further amplified when the method further includes safe sex practices. In addition, treating both seronegative and seropositive individuals can increase the likelihood of compliance and remove the stigma of HSV infection, thereby improving the likelihood of self-diagnosis and treatment among seropositive individuals.In a situation where both seropositive and seronegative individuals are taking antiviral medication, seropositive individuals no longer face stigma, and all individuals are acting to significantly reduce HSV transmission, which can significantly improve the treatment and prevention of HSV transmission, and by extension, HIV transmission.

[0070] In some embodiments, provided herein are methods for administering an antiviral composition to an HSV-seronegative individual, wherein the HSV-seronegative individual is associated with a risk category for HSV infection. In some aspects of the methods described herein, a method for preventing HSV infection in an HSV-seronegative individual includes determining the risk category of the HSV-seronegative individual. In some embodiments, an individual is associated with different HSV risk categories over a period of time. In such cases, the method of administering the antiviral composition may be adjusted to accommodate this change in risk category. For example, in some cases, an individual who is no longer in an HSV risk category discontinues use of the antiviral composition. In some cases, the HSV-seronegative individual is at risk of HSV infection due to exposure from an HSV-seropositive partner, and the HSV-seronegative individual and the HSV-seropositive individual are in a monogamous HSV-discordant relationship. In some cases, the HSV-seronegative individual is at risk of HSV infection due to exposure from an HSV-seropositive partner, and the two individuals are not in a monogamous relationship. In this case, the risk of infection may arise during one or more physical encounters with the HSV-seropositive partner. In some cases, an HSV-seronegative individual is at risk of HSV infection due to exposure from multiple HSV-seropositive partners, and the individual is not in a monogamous relationship. In this case, the risk of infection may occur during a single or multiple physical encounters with the HSV-seropositive partner. In some cases, an HSV-seronegative individual is at risk of HSV infection due to exposure from one or more partners whose HSV status is unknown, and the individual is not in a monogamous relationship. In this case, the risk of infection may occur during a single or multiple physical encounters with the one or more partners. In some embodiments, an HSV-resistant individual at risk of exposure to HSV is administered a pre-exposure composition comprising a low dose of at least one antiviral agent. In some embodiments, an HSV-resistant individual suspected of or exposed to HSV is administered a post-exposure composition comprising a high dose of at least one antiviral agent.

[0071] In some embodiments, provided herein are methods for administering an antiviral composition to an individual whose HSV serostatus is unknown. In some cases, the individual is HSV seropositive and does not know their serostatus. In other cases, the individual is HSV seropositive and does not admit to others that they are HSV seropositive. In some cases, the individual is HSV seronegative and does not know their serostatus. Not knowing or denying their serostatus may prevent an individual from warning seronegative individuals of transmission risks. In some embodiments, the methods described herein include administering to an individual whose status is unknown an amount of an antiviral agent that is effective for preventing HSV infection in HSV-seronegative subjects and for suppressive therapy of HSV in HSV-seropositive subjects. In some cases, the effective amount is a low dose of the antiviral agent. In such cases, HSV testing is not required to administer the antiviral composition. Common methods for testing HSV serostatus include immunoassays, cell culture, and nucleic acid detection, for example, using polymerase chain reaction. Currently, the standard of care does not provide for easy confirmation of HSV serostatus, as test kits are not provided that are easily performed without the assistance of a laboratory technician and medical personnel. In various embodiments, the provided methods and compositions eliminate the need to determine serostatus.

[0072] In some embodiments, the present disclosure provides a method for administering an antiviral composition to an individual with a known HSV seropositive status.The stigma associated with HSV infection can cause individuals to avoid the unpleasant conversations with doctors required for HSV testing and / or obtaining antiviral drugs.In some cases, the same dosage of antiviral drug that would be administered to an HSV seronegative individual to prevent HSV infection is administered to an HSV seropositive individual, eliminating the need for the HSV seropositive individual to acknowledge their serostatus.

[0073] In various embodiments, a method for preventing HSV infection in a seronegative individual comprises administering to the seronegative individual a composition comprising one or more antiviral agents. In some embodiments, the method comprises determining a mechanism for administering the HSV composition. In some embodiments, the method comprises determining a risk category for the HSV-seronegative individual. In some embodiments, the method comprises determining an antiviral agent dosage effective to inhibit HSV replication, HSV reactivation, or both HSV replication and HSV reactivation. In some embodiments, the method comprises determining a route of administration of the composition and a delivery mechanism, such as an oral tablet, transdermal patch, or intravaginal ring. In some embodiments, the method comprises determining an anatomical location in the individual that initiates the antiviral composition delivery mechanism. In some embodiments, the method comprises maintaining delivery of the antiviral composition to the individual for a therapeutically effective period, e.g., the delivery mechanism provides sustained or long-acting delivery of the active agent of the composition. Long-acting drug delivery mechanisms include, but are not limited to, injection devices, intravaginal rings, and transdermal patches. As a non-limiting example, the delivery mechanism is an intravaginal ring that remains within the subject and releases the active agent of the composition to the subject over a therapeutically effective period of time.

[0074] In one aspect, provided herein are compositions comprising one or more antiviral agents and methods for administering the one or more antiviral agents, wherein the compositions are administered using a long-acting delivery mechanism via a long-acting delivery device. In some embodiments, the antiviral composition is administered to an HSV-seronegative individual. In some embodiments, the antiviral composition is administered to an HSV-seropositive individual. In further embodiments, the composition is administered to both an HSV-seropositive individual and an HSV-seronegative individual, and the compositions may have the same or different active antiviral agents. In some embodiments, the long-acting delivery device is an intravaginal ring. In some embodiments, the long-acting delivery device is an injectable device. In some embodiments, the long-acting delivery device is a transdermal patch. Long-acting delivery mechanisms often provide higher average, more consistent, and / or more reliable concentrations of the antiviral drug in a subject's bloodstream over a longer period of time compared to oral administration of the same antiviral drug dosage. In some cases, administering the antiviral compositions described herein via a long-acting delivery mechanism reduces the risk of subject noncompliance. For example, the compliance of subjects receiving an antiviral composition via a long-acting drug delivery device is at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or more than that of subjects receiving an antiviral composition via an oral formulation. When administered automatically by a long-acting drug delivery device, subjects may be less likely to forget to take their medication. In some embodiments, the long-acting drug delivery device delivers an antiviral agent, such as an HSV antiviral agent, and another antiviral agent, such as one that prevents HIV. In other or additional embodiments, the long-acting drug delivery device delivers an antiviral agent and a contraceptive.

[0075] In further embodiments, the present disclosure provides methods and compositions for reducing the incidence of HSV infection, and thus the incidence of HIV infection, in seronegative individuals. In some cases, reducing the incidence of HSV infection can indirectly reduce the incidence of HIV infection. As previously discussed, HSV co-infection increases the risk of contracting HIV. This is because HSV infection creates scars and other defects in the skin, reducing the skin's effectiveness as a barrier against HIV, and because the presence of HSV activates the immune system, making the skin more vulnerable to HIV invasion. In addition, HSV has been shown to upregulate the chemokine receptor CCR5, a major co-receptor for HIV, which is suspected to be a mechanism that increases the risk of HIV transmission in HSV-positive individuals. Therefore, reducing the incidence of HSV can significantly reduce the risk of HIV infection, reducing serious medical risks and significant public health costs.

[0076] The terms "synergistic effect" and "synergistic" mean that the effect achieved with compounds used together is greater than the sum of the effects achieved when the compounds are used separately, i.e., greater than what would be expected based on the two active ingredients administered separately. A synergistic effect can be achieved when the compounds are 1) co-formulated to be administered or delivered simultaneously in a combined formulation, 2) delivered or administered in separate formulations, either alternately or in parallel, or 3) by some other regimen. When delivered / administered alternately, a synergistic effect can be achieved when the delivery / administration is performed sequentially, for example, in separate tablets, pills, capsules, or by injection using different syringes. Generally, in alternation therapy, the effective doses of each active ingredient are administered sequentially, while in combination therapy, the effective doses are administered together. A synergistic antiviral effect is an antiviral effect when the combined effect is greater than the predicted additive effect of each individual ingredient.

[0077] The term "physiologically functional derivative" refers to a pharmaceutically active compound that is equivalent to valacyclovir or famciclovir in that it has approximately the same physiological functionality when administered in combination with another pharmaceutically active compound in the combinations of the present invention. As used herein, "physiologically functional derivative" includes physiologically acceptable salts, esters, prodrugs, solvates, stereoisomers, including enantiomers and diastereomers, or stereoisomer-enriched or racemic mixtures; or any other compound capable of providing, directly or indirectly, such compound or its antivirally active metabolite or reside when administered to a subject in need thereof.

[0078] The term herpesvirus includes all alpha, beta, and gamma herpesviruses, including, but not limited to, herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), HHV-6, and HHV-7. Herpesviruses such as those listed above have been implicated in a variety of disease states, including, by way of example, neonatal herpes, herpes encephalitis, Alzheimer's disease, senile dementia, multiple sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis, juvenile idiopathic arthritis (JIA), inflammatory bowel disease, celiac disease, type 1 diabetes, chronic fatigue syndrome, and mononucleosis. Recently, it has been shown that pre-exposure treatment with valacyclovir can prevent herpes infection, including the latent stage. Therefore, treatment with valacyclovir and famciclovir, alone or in combination, will prevent herpes-related illness. The present invention provides a novel combination of two or more active ingredients that are used together.In some embodiments, synergistic antiviral effect is achieved.The term "synergistic antiviral effect" refers to an antiviral effect that is greater than the expected purely additive effect of using each antiviral component individually.

[0079] Although the active ingredients of the combination can be administered individually and separately, it is preferable to administer them as a combination.Two-component or three-component combinations can be administered simultaneously or sequentially.When administered sequentially, the combination can be administered once, twice, or three times.Preferably, two-component or three-component combinations are administered in a single pharmaceutical dosage form.Examples include a single tablet containing both valacyclovir and famcyclovir, a single tablet of valacyclovir and a single tablet of famcyclovir, two tablets of valacyclovir and a single tablet of famcyclovir, and two tablets of valacyclovir and two tablets of famcyclovir.

[0080] The compounds of the combination can be administered 1) simultaneously by combining the active ingredients in a co-formulation, or 2) alternatingly, i.e., by delivering the active ingredients sequentially, consecutively, in parallel, or simultaneously in multiple pharmaceutical formulations. In alternating therapy, a delay in administration of the second (or optionally third) compound will result in a loss of the synergistic effect of the combination. The combination can be administered either co-formulated or in alternating therapy to achieve peak plasma concentrations, such as, but not limited to, 0.001 to 200 uM. When the individual active ingredients of the combination are administered separately, they will generally each be provided in their own pharmaceutical formulation. It will be appreciated that administration of the combination of the invention in a single patient pack or patient packs of each formulation with instructions to the patient on the correct use of the invention is a desirable additional feature of the invention.

[0081] Combination therapies of the present invention include 1) a combination of valacyclovir and famciclovir, or 2) a combination containing physiologically functional derivatives of either or both thereof. The combinations can be formulated in unit dosage formulations containing a predetermined amount of the active ingredient for a regular, eg daily dose or sub-dose. Pharmaceutical formulations according to the invention comprise a combination according to the invention together with one or more pharmaceutically acceptable carriers or excipients, and optionally other therapeutic agents. The pharmaceutical formulation containing the active ingredient may be in any suitable form or may be administered in any intended manner. The combinations of the present invention can be conveniently provided as pharmaceutical formulations in unit dosage form. Convenient unit dosage formulations contain any amount of active ingredient, from 1 mg to 5 g, for example, but not limited to, from 250 mg to 1 g, of each active ingredient. The synergistic effect of valacyclovir in combination with famciclovir can be achieved over a wide range of ratios, for example, from 1:100 to 100:1 (valaciclovir:famciclovir). In certain embodiments, the ratio may range from 1:5 to 5:1, e.g., about 1:5, about 1:4, about 1:3, about 1:2, about 1:1, about 2:1, about 3:1, about 4:1, or about 5:1. In certain embodiments, the range is from about 1:2 to about 2:1. In other embodiments, approximately equal amounts of valacyclovir and famciclovir will be present. In other exemplary co-formulations, there may be more or less valacyclovir than famciclovir. Other ratios and amounts of the compounds are contemplated within the scope of the present invention.

[0082] Those skilled in the art will understand that the amount of active ingredient in the combination of the present invention required for treatment varies depending on various factors, including the nature of the condition being treated, the age and condition of the patient, and ultimately will be left to the discretion of the medical provider or treating physician.Factors include but are not limited to age, renal clearance, body weight, general condition, particularly renal function, the nature and severity of the disease to be treated.For example, cytomegalovirus (CMV) typically requires a higher dosage to achieve efficacy.

[0083] Any two of the active ingredients can be combined into a single dosage form for simultaneous or sequential administration with a third active ingredient. The three-component combination can be administered simultaneously or sequentially. When administered sequentially, the combination can be administered once, twice, or three times. The third active ingredient has anti-herpes virus activity. Exemplary third active ingredients to be administered in combination with valacyclovir and famciclovir include, but are not limited to, particularly useful third agents, such as helicase primase inhibitors, SM inhibitors, spironolactone, emtricitabine, and lamivudine, pegylated interferon, ribavirin, boceprevir, telaprevir, simeprevir, sofosbuvir, ledipasvir / sofobuvir, tenofovir, ombitasvir, paritaprevir, and ritonavir.

[0084] Formulations of the present invention suitable for oral administration may be in the form of capsules, caplets, cachets, or tablets, each containing a predetermined amount of the active ingredient as a powder or granules, as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion. The active ingredient may also be provided as a bolus, electurary, or paste. Oral tablet formulations may be coated or imprinted and may be formulated to provide slow or controlled release of the active ingredient. Tablets may also be provided with an enteric coating to provide release in parts of the intestine other than the stomach.

[0085] Viruses and viral diseases In various aspects, provided herein are methods for preventing viral infection in a subject, comprising administering to the subject a composition comprising an effective dose of at least one antiviral agent. The methods and compositions described herein relate to any infectious virus. In some embodiments, a reference to a virus is not limited to a single virus, but includes one or more infectious viruses. In exemplary embodiments, the virus is at least one herpes simplex virus (HSV). In various cases, a reference to HSV includes all infectious viruses and is not limited to herpes simplex viruses. In some embodiments, the virus is at least one human immunodeficiency virus (HIV). In some cases, the method prevents infection by both HSV and HIV. In non-limiting examples, the at least one virus includes at least one of herpesvirus, HIV-1, HIV-2, simian immunodeficiency virus (SIV), feline leukemia virus, picornavirus family, respiratory syncytial virus (RSV), influenza, adenovirus, rhinovirus, enterovirus, poliovirus, rubella virus, paramyxovirus, rotavirus, neurotropic virus, or oncovirus. In some embodiments, picornavirus family includes, but is not limited to, picornavirus, poliovirus, rhinovirus, enterovirus (coxsackievirus), hepatitis (hepatitis A virus, hepatitis B virus, hepatitis C virus), aphthovirus, parechovirus, and encephalomyocarditis virus.

[0086] In some embodiments, herpes viruses include, but are not limited to, herpes simplex virus-1, herpes simplex virus-2, varicella-zoster (VZV, i.e., chickenpox, varicella zoster, human herpesvirus 3), Epstein-Barr (human herpesvirus 4), cytomegalovirus (human herpesvirus 5), roseolovirus (human herpesviruses 6 and 7), and Karposi's sarcoma-associated herpesvirus (human herpesvirus 8). HSV-1 typically causes cold sores in infected individuals, and in some cases, genital herpes. HSV-2 typically causes genital herpes in infected individuals. Key symptoms of HSV-1 and HSV-2 include oropharyngeal infections, skin infections, eye infections, and central nervous system disorders such as meningitis and encephalitis.

[0087] Neonatal herpes simplex virus (HSV) infection affects newborn infants, resulting in high mortality and significant morbidity. Incidence estimates range from 1 / 3,000 to 1 / 20,000 live births. In most cases, parents with oral or genital herpes transmit the disorder to their offspring before, during, or shortly after birth. Signs typically occur between one and three weeks of age and rarely persist until the fourth week. Newborns may present with localized or widespread disease. Skin vesicles are common in both types, occurring in approximately 70% of cases. Newborns without skin vesicles usually present with localized CNS disease. If left untreated, newborns with isolated skin or mucosal disease often develop progressive or more severe forms of the disease within 7–10 days. Neurological infection is present in approximately one-third of neonatal HSV infections and is associated with persistent neurological abnormalities.

[0088] In some embodiments, HIV includes HIV-1 (HIV type 1), HIV-2 (HIV type 2), and SIV. HIV-1 includes, but is not limited to, extracellular viral particles and forms of HIV-1 associated with HIV-1-infected cells. In some cases, HIV-1 represents any of the known major subtypes (classes A, B, C, DE, F, G, and H), recombinant strains, or outlying subtypes (group 0), including laboratory strains and primary isolates. HIV-2 includes, but is not limited to, extracellular viral particles and forms of HIV-2 associated with HIV-2-infected cells. SIV is an HIV-like virus that infects monkeys, chimpanzees, and other non-human primates. In some embodiments, viral infection refers to the presence of viral antibodies, viral antigens, and / or viral nucleic acids in a subject, using viral diagnostic tests known to those skilled in the art (e.g., immunoassays such as ELISA, Western blot, and lateral flow assays; and PCR). In exemplary embodiments, HSV infection refers to the presence of anti-HSV antibodies or HSV nucleic acids. In some cases, an HSV seropositive individual is an individual with detectable anti-HSV antibodies in their blood. In some cases, an HSV seronegative individual is an individual without detectable anti-HSV antibodies in their blood. In some cases, an HSV seronegative individual has been exposed to HSV, but anti-HSV antibodies have not yet been detected because HSV has not established an infection and / or the individual has not yet seroconverted.

[0089] HSV-related diseases and disorders Human herpesviruses have been suggested to be involved in many diseases. Herpesviruses such as Epstein-Barr have been suggested to be involved in many autoimmune diseases and other diseases. For example, herpes simplex virus (HSV-1 and HSV-2), varicella-zoster virus (VZV), and other human herpesviruses have been suggested to be involved in Alzheimer's disease. Therefore, the compositions and methods of the present invention are useful for the treatment or prophylactic treatment of Alzheimer's disease, senile dementia, multiple sclerosis, systemic lupus erythematosus (i.e., SLE), rheumatoid arthritis, juvenile idiopathic arthritis (i.e., JIA), inflammatory bowel disease (i.e., IBD), celiac disease, type 1 diabetes, and mononucleosis, among others. Itzhaki describes the development of senile dementia and the effect of antiviral treatment in subjects with prominent, overt signs of disease caused by varicella-zoster virus (VZV) or HSV (see Itzhaki, "Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer's Disease," Frontiers in Aging Neuroscience, Vol. 10, Article 324, October 2018). Harley describes the association of EBV gene products with loci associated with risk of SLE (see Harley et al., "Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity," Nat. Genet., Vol. 50, pp. 699-707, May 2018).Chen observed an association between shingles and an increased risk of dementia, and prescription of antiviral therapy after a shingles diagnosis was associated with a reduced risk of dementia (see Chen, VC at al., "Herpes Zoster and Dementia: A Nationwide Population-Based Cohort Study," J. Clin. Psychiatry, Vol. 79, p16m11312, Jan / Feb 2018).

[0090] Epstein-Barr virus (EBV) infects 90% of humans, and although it is asymptomatic in most cases, it has the potential to cause cancer, especially in immunocompromised individuals. Immunocompromised subjects include, but are not limited to, patients with primary immunodeficiencies (see, for example, Latour et al., "Inherited Immunodeficiencies With High Predisposition to Epstein-Barr Virus-Driven Lymphoproliferative Diseases," Frontiers in Immunology, Vol. 9, pp. 1103, June 4, 2018), patients with immune dysfunction due to suppressive therapy for allogeneic transplants, and patients infected with human immunodeficiency virus (HIV). EBV-associated lymphoproliferative disorders (also called EBV+LPDs) are a group of disorders in which one or more types of lymphoid cells, namely B cells, T cells, NK cells, and histiocytic dendritic cells, become infected with Epstein-Barr virus (EBV) and hyperproliferate, leading to non-malignant, pre-malignant, and malignant lymphoproliferative disorders (LPDs).

[0091] Thus, the compositions and methods of the present invention are useful for the therapeutic or prophylactic treatment of HSV-associated disorders including, but not limited to, Alzheimer's disease, senile dementia, multiple sclerosis, systemic lupus erythematosus (i.e., SLE), rheumatoid arthritis, juvenile idiopathic arthritis (i.e., JIA), inflammatory bowel disease (i.e., IBD), celiac disease, type 1 diabetes, mononucleosis, and genetic deficiencies exemplified by, but not limited to, SH2D1A / SAP deficiency (also known as X-linked lymphoproliferative syndrome type 1, XLP-1, or Purtilo syndrome), SH2D1A / SAP deficiency (also known as X-linked lymphoproliferative syndrome type 1-XLP-1 or Purtilo syndrome), ITK deficiency, and MAGT1 deficiency.

[0092] Antiviral Composition In various aspects, provided herein are compositions and methods for preventing an HSV-seronegative subject from acquiring an HSV infection from an HSV-seropositive subject, the methods comprising administering to the HSV-seronegative subject a composition comprising an effective dose of a first antiviral agent. In various embodiments, the composition prevents the establishment of a new persistent infection in the seronegative individual after exposure to HSV. In some embodiments, the composition is administered before HSV exposure from a seropositive individual, e.g., the composition is a pre-exposure composition. In some embodiments, the composition is administered after HSV exposure from a seropositive individual, e.g., the composition is a post-exposure composition. In some embodiments, the composition is administered before and after HSV exposure to the seronegative individual.

[0093] In an additional aspect, a method for preventing an HSV-seronegative subject from contracting HSV from an HSV-seropositive individual is provided, comprising administering to the HSV-seronegative subject a composition comprising a first effective dose of a first antiviral agent, and further comprising administering to the HSV-seropositive individual a second composition comprising a second effective dose of a second antiviral agent. In some embodiments, the first antiviral agent and the second antiviral agent comprise the same active agent. In some embodiments, the first antiviral agent and the second antiviral agent comprise different active agents. In some embodiments, a composition comprising an effective dose of a first antiviral agent is useful for preventing HSV and one or more additional viral infections. In some embodiments, a composition comprising a first antiviral agent further comprises or is administered with an additional antiviral agent, which is useful for preventing HSV and / or one or more additional viral infections. Additional viral infections include, but are not limited to, HIV, HPV, hepatitis, influenza, and diseases and conditions resulting therefrom. In some embodiments, the antiviral agent in the composition for administration to an HSV-seronegative individual inactivates the HSV shed by the seropositive individual and transmitted to the HSV-seronegative individual. In some cases, the antiviral agent administered to an HSV-seronegative individual who has been exposed to HSV reduces the amount of viable virus, so that the virus cannot produce a sustainable infection in the individual. In some cases, an additional layer of protection is achieved if the HSV-seropositive partner of the HSV-seronegative individual is receiving suppressive therapy, which reduces the amount of virus transmitted to the HSV-seronegative individual.

[0094] In some embodiments, a composition useful for the method of reducing HSV viral load levels in seronegative individuals comprises two or more antiviral agents. In some cases, at least two of the two or more antiviral agents use different mechanisms to inhibit viral infection. In some cases, the antiviral agent administered to a seronegative subject is the same as the antiviral agent administered to a seropositive subject. In some cases, the antiviral agent administered to a seronegative subject is different from the antiviral agent administered to a seropositive subject. In some cases, two or more antiviral agents are administered in the same composition, or two or more antiviral agents are administered in two or more different compositions to create a cumulative effect that encompasses the effectiveness of various drugs against the target virus. For example, a combination of antiviral agents (in the same composition or in different compositions administered simultaneously) reduces the rate of viral load levels more than using one of the antiviral agents in the combination. As another example, a combination of antiviral agents reduces the rate of viral shedding and transmission more than using only one of the antiviral agents in the combination. In some cases, combination therapy is effective in situations where a single agent may not be effective due to, for example, drug resistance, medication errors, and / or noncompliance. In some cases, combinations of antiviral agents with different mechanisms of action provide enhanced therapeutic efficacy over single antiviral agents.

[0095] In some embodiments, provided herein are compositions comprising one or more antiviral agents, and methods for treating HSV and HIV seronegative individuals with the compositions to prevent HSV and / or HIV infection. In some cases, at least one of the one or more antiviral agents is an HSV antiviral agent. In some cases, at least one of the one or more antiviral agents is an HIV antiviral agent. In some cases, at least one of the one or more antiviral agents is useful for treating both HSV and HIV.

[0096] In various aspects, the present specification further provides compositions and methods for preventing pregnancy and HSV infection in HSV-seronegative subjects. In some embodiments, the method comprises administering to the subject a composition comprising a first antiviral agent and a contraceptive. In some embodiments, the method comprises administering to the subject a first composition comprising the first antiviral agent and a second composition comprising a contraceptive. In various cases, the first antiviral agent further prevents HIV infection. In some cases, the composition further comprises a second antiviral agent that prevents viral infection, such as HSV infection and / or HIV infection.

[0097] antiviral agents Various antiviral agents are useful in the methods and compositions described herein for both preventing viral transmission from seropositive individuals to seronegative individuals and preventing viral infection in seronegative individuals exposed to a virus. In some embodiments, a seronegative individual is treated with a composition comprising an antiviral agent for preventing viral infection in a seronegative individual. In exemplary embodiments, antiviral agents administered to a seronegative individual for infection prevention include those useful for acute and / or suppressive therapy in seropositive individuals. In some embodiments, antiviral agents are useful in the methods and compositions described herein for preventing HSV transmission from an HSV-seropositive individual to an HSV-seronegative individual. In some embodiments, an HSV-seronegative individual is treated with a composition comprising an antiviral agent for preventing HSV infection in a seronegative individual. In exemplary embodiments, antiviral agents administered to an HSV-seronegative individual for infection prevention include those useful for acute and / or suppressive therapy in HSV-seropositive individuals.

[0098] Antiviral agents useful in the compositions and methods described herein include, but are not limited to, any compound or pharmaceutically acceptable salt or solvate thereof that is capable of inhibiting viral replication in cells, such as cells of a subject, or that is effective in treating, preventing, or delaying the onset or progression of a viral infection or a viral disease or condition resulting from a viral infection. In some embodiments, the antiviral agent prevents or delays initial infection in an individual exposed to a virus. In some embodiments, the antiviral agent reduces the viral load in an individual infected with a virus. In some embodiments, the antiviral agent extends the asymptomatic period of a viral infection. In some embodiments, the antiviral agent maintains a low viral load in an infected patient. In some embodiments, the antiviral agent improves the overall health or quality of life of an individual infected with a virus. In some embodiments, the antiviral agent improves the life expectancy of an individual infected with a virus. In a non-limiting example, the effect of an antiviral agent on a subject is determined by, for example, comparing subjects treated with an antiviral agent with subjects not treated with an antiviral agent in a clinical trial to determine whether the antiviral agent treatment is effective in treating, preventing, or delaying the onset or progression of viral infection or viral disease or condition resulting from viral infection.In some cases, the virus is a herpes virus.In some cases, the virus is HIV.In some cases, the virus refers to more than one virus, for example, the antiviral agent administered to a subject prevents or delays infection by two or more viruses after the subject is exposed to two or more viruses.In some cases, the two or more viruses include HSV and HIV.

[0099] Suitable antiviral agents useful in the compositions and methods herein include, but are not limited to, HSV antivirals, HIV antivirals, "off-label" drugs useful for treating viral diseases or conditions, hepatitis antivirals, human papillomavirus (HPV) antivirals, and influenza antivirals. "Off-label" drugs include drugs, such as cancer agents, that are useful for treating viral infections or resulting diseases or conditions but are not currently approved for viral treatment. Antiviral agents include viral protease inhibitors, viral reverse transcriptase inhibitors, viral entry inhibitors, viral coreceptor inhibitors, viral fusion inhibitors, viral maturation inhibitors, viral integrase inhibitors, and viral immunogens. In some embodiments, the antiviral agent comprises RNA, such as siRNA, that targets viral nucleic acid. In some embodiments, the antiviral agent comprises a microbicide. In some embodiments, the antiviral agent is a component of a viral patch, such as Hansaplast® Herpes Patch SOS or Compeed® Herpes Vesicle Patch.

[0100] In some embodiments, antiviral agents useful for preventing viral diseases include those that, when administered to an individual who is seronegative for infection with a viral disease, reduce the likelihood that the seronegative individual will become infected and seropositive for the virus. For example, an effective amount of an antiviral agent administered to a seronegative subject or population of subjects, alone or in combination with one or more additional antiviral agents, reduces the risk of the subject or population of subjects becoming infected with the virus by at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100%. In some embodiments, antiviral agents useful for preventing one viral disease are also useful for preventing a second viral disease. For example, in some cases, an HIV antiviral agent used to treat an HIV-seropositive individual is also useful for administering to an HSV-seronegative individual to prevent HSV infection in the HSV-seronegative individual.

[0101] In some embodiments, the antiviral agent useful for preventing viral diseases is an HSV antiviral agent. In some cases, the viral disease is caused by a herpes virus, such as HSV. In some cases, the viral disease is caused by infection with HIV. In some cases, the antiviral agent is useful for preventing two or more viral diseases. As a non-limiting example, an HSV antiviral agent is useful for preventing HSV and HIV. In some embodiments, the HSV antiviral agent comprises an antiviral antibody, such as an anti-HSV antibody. Antibodies include monoclonal and polyclonal antibodies, including fragments and portions thereof, such as Fab fragments.

[0102] In some embodiments, the antiviral agent useful for preventing viral diseases is an HIV antiviral agent. In some cases, the viral disease is caused by a herpes virus, such as HSV. In some cases, the viral disease is caused by infection with HIV. In some cases, the viral disease is caused by a herpes virus, such as HSV. In some cases, the antiviral agent is useful for preventing two or more viral diseases. As a non-limiting example, an HIV antiviral agent is useful for preventing HSV and HIV. In some embodiments, the HIV antiviral agent includes an antiviral antibody, such as an anti-HIV antibody.

[0103] HSV antiviral agents useful in the compositions and methods described herein include nucleoside analogs that selectively target viral DNA polymerase. In some cases, the HSV antiviral agent targets thymidine kinase. For example, the HSV antiviral agent may be an analog of the natural nucleoside triphosphate dGTP, which is selectively phosphorylated by viral thymidine kinase in virus-infected cells. Phosphorylation of such analogs is minimal in uninfected cells, and cellular DNA polymerases have lower affinity for the antiviral triphosphate compared to HSV polymerase. When the analog triphosphate is incorporated into a growing DNA chain by the virus, it prevents continued chain elongation, thereby selectively inhibiting the viral DNA polymerase. Non-limiting examples of such nucleoside triphosphate analogs include acyclovir, valacyclovir, peniclovir, and famciclovir. In some cases, the HSV antiviral agent targets HSV protease. In some cases, the HSV antiviral agent inhibits the viral helicase-primase complex. A non-limiting example of a helicase-primase inhibitor is pritelivir. In some cases where a virus is resistant to nucleoside analogs, the virus may be sensitive to a helicase-primase inhibitor or a combination of a nucleoside analog and a helicase-primase inhibitor. In some cases, the compositions described herein comprise both a nucleoside analog and a helicase-primase inhibitor.

[0104] Non-limiting examples of HSV antiviral agents for use in the compositions and methods described herein include valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulations (Devirex), and others. AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, and salts, solvates, and / or combinations thereof.

[0105] In some embodiments, the antiviral agent of the compositions described herein comprises a vaccine that provides acquired immunity against diseases caused by the virus. In some cases, the composition further comprises an adjuvant. In some embodiments, described herein are compositions comprising one or more viral vaccines useful for preventing HSV transmission. In some embodiments, described herein are compositions comprising one or more viral vaccines useful for preventing HIV transmission. In some embodiments, described herein are compositions comprising one or more viral vaccines useful for preventing HSV and HIV transmission. In some cases, the viral vaccine composition further comprises or is administered together with one or more additional antiviral agents. In some cases, the viral vaccine composition further comprises or is administered together with one or more birth control methods.

[0106] In some embodiments, a viral vaccine useful for preventing one viral disease is also useful for preventing a second viral disease. For example, in some cases, an HSV vaccine is useful for preventing HIV infection in HIV-seronegative individuals. As another example, an HIV vaccine is useful for preventing HSV infection in HSV-seronegative individuals. In some cases, one or more viral vaccines are useful for preventing one or more viral diseases. As a non-limiting example, an HIV vaccine is useful for preventing HSV infection and HIV infection in seronegative individuals. As another example, an HSV vaccine is useful for preventing HSV infection and HIV infection in seronegative individuals.

[0107] Non-limiting examples of HSV vaccines useful as antiviral agents in the compositions and methods described herein include GSK208141 (gD2t, GSK glycoprotein D (gD)-Alum / 3-deacylated form of monophosphoryl lipid A), varicella zoster GSK1437173A, gD2-ASO4, Havrix™, gD-Alum, Zostavax / varicella zoster vaccine (V211, V212, V210), HSV529, HerpV (AG-707 rh-Hsc70 multivalent peptide complex), VCL-HB01, VCL-HM01, pPJV7630, GEN-003, SPL7013 gel (VivaGel™) GSK324332A, and salts, solvates, and / or combinations thereof. Non-limiting examples of HIV vaccines useful as antiviral agents in the compositions and methods described herein include GSK1492903A, VariZIG™, and Varivax.Non-limiting examples of adjuvants useful in antiviral compositions include QS-21, Matrix-M2, AlK(SO4)2, AlNa(SO4)2, AlNH4(SO4), silica, alum, Al(OH)3, Ca3(PO4)2, kaolin, carbon, aluminum hydroxide, muramyl dipeptide, N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-DMP), N-acetyl-nornuramyl-L-alanyl-D-isoglutamine (CGP11687, nor-MDP), N-acetylmuramyul-L-alanyl-D-isoglutamine (CGP11687, nor-MDP), N-acetylmuramyul-L-alanyl-D-isoglutamine (CGP11687, nor-MDP), N-acetylmuramyul-L-alanyl-D-isoglutamine (CGP11687, nor-MDP), N-acetylmuramyul-L-threon ... Soglutaminyl-L-alanine-2-(1',2'-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy)-ethylamine (CGP19835A, MTP-PE), RIBI (MPL® + TDM + CWS) 2 percent squalene / Tween-80 emulsion, lipopolysaccharide, Freund's complete adjuvant (FCA), Freund's incomplete adjuvant, Merck adjuvant 65, polynucleotides (e.g., poly IC acid and poly AU acid), Mycobacterium tuberculosis (Mycobacterium tuberculosis) These include wax D from Streptomyces tuberculosis, substances found in Corynebacterium parvum, Bordetella pertussis, and members of the Brucella genus, Titermax, ISCOMS, Quil A, ALUN, lipid A and derivatives, cholera toxin derivatives, HSP derivatives, LPS derivatives, synthetic peptide matrix or GMDP, interleukin 1, interleukin 2, and Montanide ISA-51.

[0108] In some embodiments, the antiviral agent inhibits viral entry and / or viral fusion. Examples of entry inhibitors and / or fusion inhibitors include, but are not limited to, maraviroc, enfuvirtide (T-20), vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibody, DCM205, DARPins, caprine antibodies, VIR-576, AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsin, lectin, pentafuside, and salts, solvates, and / or combinations thereof. In some embodiments, the antiviral agent is an HIV viral entry inhibitor. HIV viral entry inhibitors include, but are not limited to, CD4 receptor binding inhibitors, CD4 mimetics, gp120 mimetics, gp41 antagonists, anti-CD4 antibodies, CCR5 antagonists (e.g., zinc finger inhibitors), and CXCR4 co-receptor antagonists.

[0109] In some embodiments, the antiviral agent is an integrase inhibitor. Non-limiting examples of integrase inhibitors include dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, MK-0518, and salts, solvates, or combinations thereof.

[0110] In some embodiments, the antiviral agent is a reverse transcriptase inhibitor, such as a nucleotide reverse transcriptase inhibitor and / or a nucleoside reverse transcriptase inhibitor (NRTI). In some embodiments, the antiviral agent is a non-nucleoside reverse transcriptase inhibitor (NNRTI). NRTIs include, but are not limited to, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoporoxil fumarate, zidovudine, apricitabine, stampidine, elvucitabine, rasvir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine ddC, azidothymidine, tenofovir alafenamide fumarate, entecavir, and salts, solvates, and / or combinations thereof. NNRTIs include, but are not limited to, delavirdine, efavirenz, etravirine (TMC-125), nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, adefovir, dapivirine, lersivirine, and salts, solvates, and / or combinations thereof. Further non-limiting examples of reverse transcriptase inhibitors include alovudine, elvucitabine, TMC-278, DPC-083, amdoxovir, (-)-beta-D-2,6-diamino-purine dioxolane, MIV-210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC-278, KP1461, KP-1212, rhodenosine (FddA), 5-[(3,5- dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamic acid, (-)-I2-D-2,6-diaminopurine dioxolane, AVX-754, BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4-dihydro-4-trifluoromethyl-2(1H)-quinazolinone), TMC-120, L697639, and salts, solvates, and / or combinations thereof.

[0111] In some embodiments, the antiviral agent is a protease inhibitor. Non-limiting examples of protease inhibitors include atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir (SC-52151), droxinavir, Emtriva, Invirase, Agenerase, TMC-126, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, and KNI-27. 2, DPC-681, DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), and salts, solvates, and / or combinations thereof.

[0112] In some embodiments, the antiviral agent is a bactericide. Non-limiting examples of bactericides include surfactants such as nonoxynol-9, sodium dodecyl sulfate, and Savvy (1.0% C31G). In some embodiments, the bactericide, e.g., BufferGel®, lowers the pH of vaginal secretions. In some embodiments, the antiviral agent comprises a polyanionic bactericide. An example of a polyanionic bactericide is carrageenan. Carrageenan is a linear sulfated polysaccharide that can act as a decoy receptor for virus binding, as viruses use it for initial attachment to cell membranes. In some embodiments, the bactericide is a nanoscale dendrimer molecule that binds to viruses. An example of a nanoscale dendrimer molecule is the active ingredient in VivaGel®. An additional example of a bactericide is PRO-2000, also known as PRO2000 / 5, naphthalene 2-sulfonate polymer, or polynaphthalene sulfonate.

[0113] In some embodiments, the composition comprises an active agent that is used as an antiviral "off-label" drug to treat or prevent a viral infection. In some cases, the composition is administered in conjunction with the "off-label" drug. Non-limiting examples of "off-label" drugs useful with or in the compositions provided herein include amphotericin B, sulfamethoxazole, trimethoprim, clarithromycin, daunorubicin, fluconazole, doxorubicin, anidulafungin, immunoglobulins, gamma globulins, dronabinol, megestrol acetate, atovaquone, rifabutin, pentamidine, trimetrexate glucuronate, leucovorin, alitretinoin gel, erythropoietin, calcium hydroxyapatite, poly-L-lactic acid, somatropin rDNA, itraconazole, paclitaxel, voriconazole, cidofovir, fomivirsen, azithromycin, and salts, solvates, and / or combinations thereof. In some embodiments, the antiviral agent is a cancer drug, such as ruxolitinib or tocilizumab.

[0114] In some embodiments, the composition for preventing or treating a viral infection comprises at least one of the following antiviral agents: bevirimat, TRIM5alpha, Tat antagonist, trichosanthin, abzyme, calanolide A, ceragenin, cyanovirin-N, diarylpyrimidine, epigallocatechin gallate (EGCG), foscarnet, griffithsin, hydroxycarbamide, miltefosine, portmanteaus. nteau inhibitors, scytovirin, seliciclib, synergistic enhancer, tre recombinase, zinc finger protein transcription factor, KP-1461, BIT225, aplaviroc, atevirdine, brecanavir, capravirin, dexerubucitabine, emivirine, lersivirine, rhodenosine, loviride, fomivirsen, glycyrrhizic acid (anti-inflammatory, 111 beta-hydroxysteroid dehydrogenase (1 beta-hydroxysteroid dehydrogenase), zinc salts, cellulose sulfate, cyclodextrin, dextrin-2-sulfate, NCP7 inhibitors, AMD-3100, BMS-806, BMS-793, C31G, carrageenan, CD4-IgG2, cellulose acetate phthalate, mAb 2G12, mAb b12, Merck 167, plant lectins, polynaphthalene sulfate, polysulfo-styrene, PRO2000, PSC-Rantes, SCH-C, SCH-D, T-20, TMC-125, UC-781, UK-427, UK-857, or salts, solvates, or combinations thereof.

[0115] In some embodiments, the composition for preventing or treating a viral infection comprises at least one of the following antiviral agents: Carraguard (PC-515), brincidofovir (CMX001), zidovudine, virus-specific cytotoxic T cells, idoxuridine, podophyllotoxin, rifampicin, methisazone, interferon alfa 2b (Intron-A), pegylated interferon alfa-2a, ribavirin, moroxydine, pleconaril, BCX4430, taribavirin (viramidine, ICN3142), favipiravir, lintatolimod, ibasitabine (5-iodo-2'- deoxycytidine), methisazone (metisazone), ampligen, arbidol, Atripla®, combivir, imunovir, nexavir, trizivir, truvada, lamivudine, dideoxyadenosine, floxuridine, idozuridine, inosine pranobex, 2'-deoxy-5-(methylamino)uridine, digoxin, imiquimod, interferon type III, interferon type II, interferon type I, tea tree oil, or a salt, solvate, or combination thereof.

[0116] In some embodiments, a composition for preventing or treating a viral infection comprises a hepatitis antiviral agent including tenofovir, glycyrrhizinic acid, fialuridine, telbivudine, adefovir, entecavir, lamivudine, clevudine, asunaprevir, boceprevir, faldaprevir, grazoprevir, paritaprevir, ritonavir, telaprevir, simeprevir, sofosbuvir, ACH-3102, daclatasvir, deleofvir, elbasvir, ledipasvir, MK-3682, MK-8408, samatasvir, ombitasvir, entecavir, or a salt, solvate, or combination thereof.

[0117] In some embodiments, a composition for preventing or treating a viral infection comprises an influenza antiviral including elderberry sambucus, umifenovir, amantadine, rimantadine, oseltamivir, zanamivir, peramivir, laninamivir, or a salt, solvate, or combination thereof. In some embodiments, a composition for preventing or treating a viral infection comprises an HPV antiviral agent comprising a pyrrole polyamide, lopinavir, carrageenan, zinc, or a salt, solvate, or combination thereof.

[0118] In some embodiments, a composition comprising an antiviral agent in combination with at least one additional active agent, where the combination refers to a composition comprising a combination of two or more active agents, or a composition comprising an antiviral agent administered in combination with one or more additional active agents. In some cases, the combination of active agents produces a synergistic effect on antiviral activity. In one example, the synergistic effect can be calculated using the sigmoid-Emax equation, the Loewe equation, and the median effect equation.

[0119] In some embodiments, a composition comprising an antiviral agent useful for preventing and / or treating a viral disease further comprises or is administered in combination with another drug or active agent for preventing and / or treating a viral disease. In some cases, the composition comprises or is administered together with a vaccine, a gene therapy treatment, a cytokine, a TAT inhibitor, an immunomodulator, or a combination thereof. In some cases, the composition comprises or is administered together with an anti-infective agent, including an antifungal agent, an antibacterial agent, an antiprotozoal agent, or a combination thereof. In some cases, the composition comprises or is administered with an immunomodulatory agent, such as pentamidine isethionate, autologous CD8+ infusion, gamma-interferon immunoglobulin, thymic peptide, IGF-I, anti-Leu3A, autologous vaccination, biostimulation, extracorporeal photophoresis, cyclosporine, rapamycin, FK-565, FK-506, GCSF, GM-CSF, hyperthermia, isoprinosine, rVIG, HIVIG, passive immunotherapy, and polio vaccine hyperimmunization, or a combination thereof. In some embodiments, the composition comprises or is administered with a pharmacokinetic enhancer, such as cobicistat. In some embodiments, the composition comprises or is administered with a synergistic enhancer, such as chloroquine / quinoline enhancers of protease inhibitors, CYP3A4, hydroxyurea, leflunomide, mycophenolic acid, resveratrol, or a combination thereof.

[0120] In some embodiments, compositions useful in the methods described herein comprise a combination of active agents, at least one of which is an antiviral agent. Examples of combinations include, but are not limited to, maraviroc and emtricitabine; maraviroc, emtricitabine, and raltegravir; raltegravir and emtricitabine; raltegravir and lamivudine; abacavir and lamivudine; abacavir, dolutegravir, and lamivudine; abacavir, lamivudine, and zidovudine; atazanavir and cobicistat; darunavir and cobicistat; efavirenz, emtricitabine, and tenocycline. elvitegravir, cobicistat, emtricitabine, and tenofovir; emtricitabine, rilpivirine, and tenofovir; lamivudine and raltegravir; lamivudine and zidovudine; lopinavir and ritonavir; emtricitabine and tenofovir disoproxil fumarate; lamivudine and zidovudine; lopinavir and ritonavir; inosine, acetamidobenzoic acid, and dimethylaminoisopropanol; and salts, solvates, and / or combinations thereof.

[0121] In some embodiments, compositions useful in the methods described herein for preventing a viral infection (e.g., HSV) in a seronegative subject and / or for treating a viral infection (e.g., HSV suppressive treatment) in a seropositive subject comprise one or more of the following active agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimo (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, GSK208141 (gD2t, GSK glycoprotein D (gD)-Alum / 3-deacylated monophosphoryl lipid A), varicella-zoster GSK1437173A, gD2-ASO4, Havrix™, gD-Alum, Zostavax / varicella-zoster vaccine (V211, V212, V210), HSV529, HerpV (AG-707 rh-Hsc70 multivalent peptide complex), VCL-HB01, VCL-HM01, pPJV7630, GEN-003, SPL7013 gel (VivaGel™) GSK324332A, GSK1492903A, VariZIG™, and Varivax, maraviroc, enfuvirtide, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibody, DCM205, DARPins, caprine antibody, VIR-576, enfuvirtide (T-20), AMD11070, PR0542,SCH-C, T-1249, cyanovirin, griffithsen, lectin, pentafuside, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, MK-0518, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasvir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine (TMC-125), nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, adefovir ru, dapivirine, lersivirine, alovudine, elvucitabine, TMC-278, DPC-083, amdoxovir, (-)-beta-D-2,6-diamino-purine dioxolane, MIV-210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC-278, KP1461, KP -1212, rhodenosine (FddA), 5-[(3,5-dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamate, (-)-I2-D-2,6-diaminopurine dioxolane, AVX-754, BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4-dihydro-4-trifluoromethyl-2 (1H)-quinazolinone), TMC-120, L697639, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir (SC-52151), droxinavir, Emtriva, Invirase, Agenerase, TMC-126, mozenavir (DMP-450), JE-2147 (AG1776), L-756423,KNI-272, DPC-681, DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), nonoxynol-9, sodium dodecyl sulfate, Savvy (1.0% C31G), BufferGel®, carrageenan, VivaGel®, PRO2000 / 5, Na PRO-2000, also known as phthalene 2-sulfonate polymer or polynaphthalene sulfonate, amphotericin B, sulfamethoxazole, trimethoprim, clarithromycin, daunorubicin, fluconazole, doxorubicin, anidulafungin, immunoglobulins, gamma globulins, dronabinol, megestrol acetate, atovaquone, rifabutin, pentamidine, trimetrexate glucuronate, leucovorin, alitretinoin gel, erythropoietin, calcium hydroxide Cyapatite, poly-L-lactic acid, somatropin rDNA, itraconazole, paclitaxel, voriconazole, cidofovir, fomivirsen, azithromycin, ruxolitinib, tocilizumab, bevirimat, TRIM5 alpha, Tat antagonist, trichosanthin, abzyme, calanolide A, ceragenin, cyanovirin-N, diarylpyrimidine, epigallocatechin gallate (EGCG), foscarnet, griffithsin, hydroxycarbamide, miltefosine, portmanteaus inhibitor, sitovirin, seliciclib, synergistic enhancer -, tre recombinase, zinc finger protein transcription factor, KP-1461, BIT225, aplaviroc, atevirdine, brecanavir, capravirine, dexelbucitabine, emivirine, lersivirine, rhodenosine, loviride, fomivirsen, glycyrrhizic acid (anti-inflammatory, inhibits 11 beta-hydroxysteroid dehydrogenase), zinc salt, cellulose sulfate, cyclodextrin, dextrin-2-sulfate, NCP7 inhibitor, AMD-3100, BMS-806, BMS-793, C31G, carrageenan, CD4-IgG2,Cellulose acetate phthalate, mAb 2G12, mAb b12, Merck167, plant lectin, polynaphthalene sulfate, polysulfo-styrene, PRO2000, PSC-Rantes, SCH-C, SCH-D, T-20, TMC-125, UC-781, UK-427, UK-857, Caraguard (PC-515), brincidofovir (CMX001), zidovudine, virus-specific cytotoxic T cells, idoxuridine, podophyllotoxin, rifampicin, methisazone, interferon alpha 2b (Intron- A), peginterferon alfa-2a, ribavirin, moroxydine, pleconaril, BCX4430, taribavirin (viramidine, ICN3142), favipiravir, lintatolimod, ibasitabine (5-iodo-2'-deoxycytidine), methisazone, Amplifyn, arbidol, Atripla®, Combivir, Immunovir, Nexavir, Trizivir, Truvada, lamivudine, dideo Oxyadenosine, floxuridine, idoxuridine, inosine pranobex, 2'-deoxy-5-(methylamino)uridine, digoxin, imiquimod, interferon type III, interferon type II, interferon type I, tea tree oil, glycyrrhizinic acid, fialuridine, telbivudine, adefovir, entecavir, lamivudine, clevudine, asunaprevir, boceprevir, faldaprevir, grazoprevir In some embodiments, the composition further comprises and / or is administered in conjunction with one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral.It may further comprise and / or be administered in conjunction with one or more contraceptive agents.

[0122] In some embodiments, compositions useful in the methods described herein for preventing HSV infection in a seronegative subject and / or treating HSV in a seropositive subject comprise one or more of the following antiviral agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (a mixture of ethanol and glycolic acid), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or a salt, solvate, or combination thereof. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more contraceptive agents.

[0123] In some embodiments, compositions useful in the methods described herein for preventing a viral infection (e.g., HSV) in a seronegative subject and / or treating a viral infection (e.g., HSV suppressive treatment) in a seropositive subject comprise two, three, four, five, or more of the following active agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimo (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, GSK208141 (gD2t, GSK glycoprotein D (gD)-Alum / 3-deacylated monophosphoryl lipid A), varicella-zoster GSK1437173A, gD2-ASO4, Havrix™, gD-Alum, Zostavax / varicella-zoster vaccine (V211, V212, V210), HSV529, HerpV (AG-707 rh-Hsc70 multivalent peptide complex), VCL-HB01, VCL-HM01, pPJV7630, GEN-003, SPL7013 gel (VivaGel™) GSK324332A, GSK1492903A, VariZIG™, and Varivax, maraviroc, enfuvirtide, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibody, DCM205, DARPins, caprine antibody, VIR-576, enfuvirtide (T-20),AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsen, lectin, pentafuside, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, MK-0518, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasvir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine (TMC-125), nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epinephrine Virucivir, adefovir, dapivirine, lersivirine, alovudine, elvucitabine, TMC-278, DPC-083, amdoxovir, (-)-beta-D-2,6-diamino-purine dioxolane, MIV-210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC- 278, KP1461, KP-1212, rhodenosine (FddA), 5-[(3,5-dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamate, (-)-I2-D-2,6-diaminopurine dioxolane, AVX-754, BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4 -dihydro-4-trifluoromethyl-2(1H)-quinazolinone), TMC-120, L697639, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir (SC-52151), droxinavir, Emtriva, Invirase, Agenerase, TMC-126, mozenavir (DMP-450),JE-2147 (AG1776), L-756423, KNI-272, DPC-681, DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), nonoxynol-9, sodium dodecyl sulfate, Savvy (1.0% C31G), BufferGel®, carrageenan , VivaGel®, PRO2000 / 5, PRO-2000, also known as naphthalene 2-sulfonate polymer or polynaphthalene sulfonate, amphotericin B, sulfamethoxazole, trimethoprim, clarithromycin, daunorubicin, fluconazole, doxorubicin, anidulafungin, immunoglobulins, gamma globulins, dronabinol, megestrol acetate, atovaquone, rifabutin, pentamidine, trimetrexate glucuronate, leucovorin, alitretinoin gel, erythropoietin (erythropoeetin), calcium hydroxyapatite, poly-L-lactic acid, somatropin rDNA, itraconazole, paclitaxel, voriconazole, cidofovir, fomivirsen, azithromycin, ruxolitinib, tocilizumab, bevirimat, TRIM5 alpha, Tat antagonist, trichosanthin, abzyme, calanolide A, ceragenin, cyanovirin-N, diarylpyrimidine, epigallocatechin gallate (EGCG), foscarnet, griffithsin, hydroxycarbamide, miltefosine, portomante Au inhibitors, sitovirine, seliciclib, synergistic enhancer, tre recombinase, zinc finger protein transcription factor, KP-1461, BIT225, aplaviroc, atevirdine, brecanavir, capravirine, dexerubucitabine, emivirine, lersivirine, rhodenosine, loviride, fomivirsen, glycyrrhizic acid (anti-inflammatory, inhibits 11beta-hydroxysteroid dehydrogenase), zinc salts, cellulose sulfate, cyclodextrin, dextrin-2-sulfate, NCP7 inhibitors, AMD-3100, BMS-806,BMS-793, C31G, carrageenan, CD4-IgG2, cellulose acetate phthalate, mAb 2G12, mAb b12, Merck167, plant lectin, polynaphthalene sulfate, polysulfo-styrene, PRO2000, PSC-Rantes, SCH-C, SCH-D, T-20, TMC-125, UC-781, UK-427, UK-857, Caraguard (PC-515), brincidofovir (CMX001), zidovudine, virus-specific cytotoxic T cells, idoxuridine, podophyllotoxin, rifampicin, methisazone, interferon alpha 2b (Intron- A), peginterferon alfa-2a, ribavirin, moroxydine, pleconaril, BCX4430, taribavirin (viramidine, ICN3142), favipiravir, lintatolimod, ibasitabine (5-iodo-2'-deoxycytidine), methisazone, Amplifyn, arbidol, Atripla®, Combivir, Immunovir, Nexavir, Trizivir, Truvada, lamivudine, dideo Oxyadenosine, floxuridine, idoxuridine, inosine pranobex, 2'-deoxy-5-(methylamino)uridine, digoxin, imiquimod, interferon type III, interferon type II, interferon type I, tea tree oil, glycyrrhizinic acid, fialuridine, telbivudine, adefovir, entecavir, lamivudine, clevudine, asunaprevir, boceprevir, faldaprevir, grazoprevir In some embodiments, the composition further comprises one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral, such as an HIV antiviral, ...and / or administered in conjunction with one or more contraceptive agents. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more contraceptive agents.

[0124] In some embodiments, compositions useful in the methods described herein for preventing HSV infection in a seronegative subject and / or treating HSV in a seropositive subject comprise two, three, four, five, or more of the following antiviral agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (a mixture of ethanol and glycolic acid), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or a salt, solvate, or combination thereof. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more contraceptive agents.

[0125] In some embodiments, compositions useful in the methods described herein for preventing a viral infection (e.g., HSV) in a seronegative subject and / or for treating a viral infection (e.g., HSV suppressive treatment) in a seropositive subject comprise one or more of the following active agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex), AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or their salts or solvates or combinations thereof, and one or more of the following active agents: maraviroc, enfuvirtide, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibodies, DCM205, DARPins, caprin antibodies, VIR-576, enfuvirtide (T-20), AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsen, lectin, pentafuside, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, B 1224436, cabotegravir, GSK1265744, GSK-572, MK-0518, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasibir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine (TMC-125), nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, adefovir, dapivirine, lersivirine, alovudine, elvucitabine, TMC-278, DPC-083, amdoxovir, (-)-beta-D-2,6-diamino-purine dioxolane, MIV -210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC-278, KP1461, KP-1212, rhodenosine (FddA), 5-[(3,5-dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamate, (-)-I2-D-2,6-diaminopurine dioxolane, AVX-754, BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4-dihydro-4-trifluoromethyl-2(1H)-quinazolinone), TMC-120, L697639, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir (SC-52151), droxinavir, Emtriva, Invirase, Agenerase, TMC-126, mozenavir (DMP-450), JE-2147 (AG1776), L The compositions may comprise one or more of: -756423, KNI-272, DPC-681, DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), or salts, solvates, or combinations thereof. In some embodiments, the compositions further comprise and / or are administered in conjunction with one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral. In some embodiments, the compositions further comprise and / or are administered in conjunction with one or more contraceptive agents.

[0126] In some embodiments, the compositions useful in the methods described herein for preventing HSV infection in a seronegative subject and / or treating HSV in a seropositive subject contain one or more of the following active agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or salts, solvates, or combinations thereof Two, three, four, five, or more of the following active agents are present: maraviroc, enfuvirtide, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibodies, DCM205, DARPins, caprin antibodies, VIR-576, enfuvirtide (T-20), AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsen, lectin, pentafuside, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, B 1224436, cabotegravir, GSK1265744, GSK-572, MK-0518, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasibir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine (TMC-125), nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, adefovir, dapivirine, lersivirine, alovudine, elvucitabine, TMC-278, DPC-083, amdoxovir, (-)-beta-D-2,6-diamino-purine dioxolane, MIV -210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC-278, KP1461, KP-1212, rhodenosine (FddA), 5-[(3,5-dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamate, (-)-I2-D-2,6-diaminopurine dioxolane, AVX-754, BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4-Dihydro-4-trifluoromethyl-2(1H)-quinazolinone), TMC-120, L697639, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir, Lopinavir, Amprenavir, Telenavir (SC-52151), Droxinavir, Emtriva, Invirase, Agenerase, TMC-126, Mozenavir (DMP-450), JE-2147 (AG1776), L-756423 , KNI-272, DPC-681, DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), or salts, solvates, or combinations thereof. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more additional antiviral agents, such as an HSV antiviral and / or an HIV antiviral. In some embodiments, the composition further comprises and / or is administered in conjunction with one or more contraceptive agents.

[0127] contraceptives In various aspects, provided herein are compositions comprising one or more antiviral agents, and methods for preventing viral infection in individuals who are seronegative for a virus, comprising administering one or more antiviral agents in combination with one or more contraceptive agents to the seronegative individual. In some cases, the antiviral composition further comprises one or more contraceptive agents. In some cases, the antiviral composition is administered together with one or more contraceptive agents. In some embodiments, provided herein are pre-exposure compositions comprising one or more contraceptive agents. In some cases, the pre-exposure composition is administered together with one or more contraceptive agents. In some embodiments, provided herein are post-exposure compositions comprising one or more contraceptive agents. In some cases, the post-exposure composition is administered together with one or more contraceptive agents. In further embodiments, provided herein are compositions for treating individuals who are seropositive for a virus, comprising one or more antiviral agents and one or more contraceptive agents. In still further embodiments, provided herein are compositions for treating an individual who is seropositive for a virus, comprising one or more antiviral agents, wherein the one or more antiviral agents are administered in conjunction with one or more contraceptive agents.

[0128] In various aspects, provided herein are compositions comprising one or more antiviral agents and methods for preventing HSV infection in an HSV-seronegative individual, comprising administering to the seronegative individual one or more antiviral agents in combination with one or more contraceptive agents. In some embodiments, the one or more antiviral agents are HSV antiviral agents. In some embodiments, the one or more antiviral agents are HIV antiviral agents. In some embodiments, one or more of the antiviral agents treat or prevent HSV, HIV, or both HSV and HIV. In some cases, the antiviral composition further comprises one or more contraceptive agents. In some cases, the antiviral composition is administered in conjunction with one or more contraceptive agents. In some embodiments, provided herein are HSV pre-exposure compositions comprising one or more contraceptive agents. In some cases, the HSV pre-exposure compositions are administered in conjunction with one or more contraceptive agents. In some embodiments, provided herein are HSV post-exposure compositions comprising one or more contraceptive agents. In some cases, the HSV post-exposure composition is administered together with one or more contraceptive agents.In a further embodiment, provided herein is a composition for treating an HSV seropositive individual, comprising one or more antiviral agents and one or more contraceptive agents.In yet a further embodiment, provided herein is a composition for treating an HSV virus seropositive individual, comprising one or more antiviral agents, wherein the one or more antiviral agents are administered together with one or more contraceptive agents.

[0129] In some embodiments, compositions useful in the methods described herein for preventing pregnancy in seronegative subjects and for preventing HSV infection comprise one, two, three, four, or more antiviral agents and one, two, three, four, or more contraceptive agents. In some embodiments, compositions useful in the methods described herein for preventing pregnancy in HSV and HIV seronegative subjects and for preventing HSV and HIV infection comprise one, two, three, four, or more antiviral agents and one, two, three, four, or more contraceptive agents. In some embodiments, compositions useful in the methods described herein for preventing pregnancy in seronegative subjects and for preventing HSV infection comprise one, two, three, four, or more antiviral agents, and the compositions are administered with one, two, three, four, or more contraceptive agents. In some embodiments, compositions useful in the methods described herein for preventing pregnancy and for preventing HSV and HIV infection in HSV- and HIV-seronegative subjects comprise one, two, three, four, or more antiviral agents, and the compositions are administered with one, two, three, four, or more contraceptive agents.

[0130] In some embodiments, contraceptive agents refer to active agents that prevent conception or pregnancy. Non-limiting examples of contraceptive agents useful in the compositions and methods provided herein include 17a-ethynyl-levonorgestrel-17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, ethinylestradiol, levonorgestrel, medroxyprogesterone acetate, nestrone, norethindrone, ethynodiol diacetate, RU486, N9, mifepristone, mifegin, mifeprex, 17a-ethynyl-levonorgestrel. levongestrel, 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, megestrol, etono-progestin alonegestrel, and 17-acetoxy-16-methylene-19-norprogesterone, and salts, solvates, and / or combinations thereof.

[0131] In some cases, a reference to a contraceptive agent includes a physical barrier that prevents conception or pregnancy. In some cases, the physical barrier is a condom, a cervical cap, a female condom, or a diaphragm. In some cases, the contraceptive agent is an intrauterine device. In some cases, the contraceptive agent is a spermicide (e.g., nonoxynol, octoxynol). In some cases, the contraceptive agent is an emergency contraceptive agent that is administered, for example, in high doses, after unprotected sexual activity. Non-limiting examples of emergency contraceptive agents include levonorgestrel; a combination of estrogen and progestin; progestin, antiprogestin (e.g., ulipristal acetate, mifepristone), and salts, solvates, or combinations thereof. In some cases, the contraceptive agent is administered in combination with the post-exposure composition described herein, and the contraceptive agent and the post-exposure composition are configured to be administered after unprotected sexual activity.

[0132] In some embodiments, compositions useful in the methods described herein for preventing pregnancy and for preventing viral infection (e.g., HSV) in seronegative subjects comprise: a) one or more of the following active agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimo (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, GSK208141 (gD2t, GSK glycoprotein D (gD)-Alum / 3-deacylated monophosphoryl lipid A), varicella-zoster GSK1437173A, gD2-ASO4, Havrix™, gD-Alum, Zostavax / varicella-zoster vaccine (V211, V212, V210), HSV529, HerpV (AG-707rh-Hsc70 multivalent peptide complex), VCL-HB01, VCL-HM01, pPJV7630, GEN-003, SPL7013 gel (VivaGel™), GSK324332A, GSK1492903A, VariZIG™, and Varivax, maraviroc, enfuvirtide, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibody, DCM205, DARPins, caprine antibody, VIR -576, enfuvirtide (T-20), AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsen, lectin, pentafuside, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, MK-0518, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasibir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine (TMC-125), nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, adefovir, dapivirine, lersivirine, alovudine, elvucitabine, TMC-278, DPC-08 3, amdoxovir, (-)-beta-D-2,6-diamino-purine dioxolane, MIV-210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC-278, KP1461, KP-1212, rhodenosine (FddA), 5-[(3,5-dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamate, (-)-12-D-2,6-Diaminopurine dioxolane, AVX-754, BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4-dihydro-4-trifluoromethyl-2(1H)-quinazolinone), TMC-120, L697639, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir (SC-52151), droxinavir, Emtriva, Invirase, Agenerase , TMC-126, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, KNI-272, DPC-681, DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), nonoxynol-9, sodium dodecyl sulfate, Savvy (1.0% C31 G), BufferGel®, carrageenan, VivaGel®, PRO2000 / 5, PRO-2000, also known as naphthalene 2-sulfonate polymer or polynaphthalene sulfonate, amphotericin B, sulfamethoxazole, trimethoprim, clarithromycin, daunorubicin, fluconazole, doxorubicin, anidulafungin, immunoglobulins, gamma globulins, dronabinol, megestrol acetate, atovaquone, rifabutin, pentamidine, trimetrexate glucuronate, and lorlatin. Icovorin, alitretinoin gel, erythropoietin, calcium hydroxyapatite, poly-L-lactic acid, somatropin rDNA, itraconazole, paclitaxel, voriconazole, cidofovir, fomivirsen, azithromycin, ruxolitinib, tocilizumab, bevirimat, TRIM5 alpha, Tat antagonist, trichosanthin, abzyme, calanolide A, ceragenin, cyanovirin-N, diarylpyrimidine, epigallocatechin gallate (EGCG), foscarnet, griffithsin,Hydroxycarbamide, miltefosine, portmanteaus inhibitor, sitovirine, seliciclib, synergistic enhancer, tre recombinase, zinc finger protein transcription factor, KP-1461, BIT225, aplaviroc, atevirdine, brecanavir, capravirin, dexerubucitabine, emivirine, lersivirine, rhodenosine, loviride, fomivirsen, glycyrrhizic acid (anti-inflammatory, inhibits 11beta-hydroxysteroid dehydrogenase), zinc salt, cellulose sulfate, cyclodextrin, dextrin-2-sulfate, NCP7 inhibitor, AMD-3100, BMS-806, BMS-793, C31G, carrageenan, CD4-IgG2, cellulose acetate phthalate, mAb 2G12, mAb b12, Merck167, plant lectin, polynaphthalene sulfate, polysulfo-styrene, PRO2000, PSC-Rantes, SCH-C, SCH-D, T-20, TMC-125, UC-781, UK-427, UK-857, Caraguard (PC-515), brincidofovir (CMX001), zidovudine, virus-specific cytotoxic T cells, idoxuridine, podophyllotoxin, rifampicin, methisazone, interferon alfa-2b (Intron-A), pegylated interferon alfa-2a, ribavirin, moroxydine, pleconaril, BCX4430, taribavirin (viramidine, ICN3142), favipiravir, lintatolimod, ibacitabine (5-iodo-2'-deoxycytidine), methisazone (m ethisazone) (metisazone), Amplgen, arbidol, Atripla®, Combivir, Immunovir, Nexavir, Trizivir, Truvada, lamivudine, dideoxyadenosine, floxuridine, idozuridine, inosine pranobex, 2'-deoxy-5-(methylamino)uridine, digoxin, imiquimod, interferon type III, interferon type II, interferon type I, tea tree oil, glycyrrhizinic acid, fialuridine, telbivudine, adefovir, entecavir, lamivudine, clevudine, asunaprevir, boceprevir, faldaprevir, grazoprevir, paritaprevir, ritonavir, telaprevir,simeprevir, sofosbuvir, ACH-3102, daclatasvir, deleobuvir, elbasvir, ledipasvir, MK-3682, MK-8408, samatasvir, ombitasvir, entecavir, elderberry sambux, umifenovir, amantadine, rimantadine, oseltamivir, zanamivir, peramivir, laninamivir, pyrrole polyamides, lopinavir, or salts, solvates, or combinations thereof; and b) one or more of the following active agents: 17a-ethynyl-levonorgestrel-17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, ethinyl estradiol, levonorgestrel, methyl acetate The composition may comprise one or more of the following active agents: droxyprogesterone, nestrone, norethindrone, ethynodiol diacetate, RU486, N9, mifepristone, mifegin, mifeprex, 17a-ethynyl-levonorgestrel, 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, megestrol, etono-progestin alonegestrel, and 17-acetoxy-16-methylene-19-norprogesterone, or salts, solvates, or combinations thereof. In some embodiments, the composition is a pre-exposure composition containing a low dose of one or more active agents. In some embodiments, the composition is a post-exposure composition containing a high dose of one or more active agents. In some embodiments, the composition further prevents and / or treats HIV infection. In some embodiments, the composition is further administered with one or more HIV antivirals to prevent and / or treat HIV. In some embodiments, the composition further comprises or is administered with one or more additional contraceptive agents.

[0133] In some embodiments, compositions useful in the methods described herein for preventing pregnancy and treating viral infections (e.g., HSV suppressive therapy) in seropositive subjects comprise a) one or more of the following active agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex), AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimo (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, GSK208141 (gD2t, GSK glycoprotein D (gD)-Alum / 3-deacylated monophosphoryl lipid A), varicella-zoster GSK1437173A, gD2-ASO4, Havrix™, gD-Alum, Zostavax / varicella-zoster vaccine (V211, V212, V210), HSV529, HerpV (AG-707 rh-Hsc70 multivalent peptide complex), VCL-HB01, VCL-HM01, pPJV7630, GEN-003, SPL7013 gel (VivaGel™), GSK324332A, GSK1492903A, VariZIG™, and Varivax, maraviroc, enfuvirtide, vicriviroc, cenicriviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibody, DCM205, DARPins, caprine antibody, VIR-576, enfuvirtide (T-20), AMD11070, PR0542, SCH-C, T-1249, cyanovirin,Griffithsen, lectin, pentafuside, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, MK-0518, abacavir, didanosine, emtrictabine, lamivudine, stavudine, tenofovir, tenofovir disoproxil fumarate fumarate), zidovudine, apricitabine, stampidine, elvucitabine, rasibir, amdoxovir, stavudine, zalcitabine, festinavir, dideoxycytidine (ddC), azidothymidine, tenofovir alafenamide fumarate, entecavir, delavirdine, efavirenz, etravirine (TMC-125), nevirapine, rilpivirine, doravirine, calanolide A, capravirine, epivir, adefovir, dapivir Viridine, lersivirine, alovudine, elvucitabine, TMC-278, DPC-083, amdoxovir, (-)-beta-D-2,6-diamino-purine dioxolane, MIV-210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC-278, KP1461, KP-1212, rode Nosine (FddA), 5-[(3,5-dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamic acid, (-)-I2-D-2,6-diaminopurine dioxolane, AVX-754, BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4-dihydro-4-trifluoromethyl-2(1H)-quinazolinone) , TMC-120, L697639, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir (SC-52151), droxinavir, Emtriba, Invirase, Agenerase, TMC-126, mozenavir (DMP-450), JE-2147 (AG1776), L-756423, KNI-272, DPC-681,DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), nonoxynol-9, sodium dodecyl sulfate, Savvy (1.0% C31G), BufferGel®, carrageenan, VivaGel®, PRO2000 / 5, naphthalene 2-sulfonate polymer or PRO-2000, also known as polynaphthalenesulfonate, amphotericin B, sulfamethoxazole, trimethoprim, clarithromycin, daunorubicin, fluconazole, doxorubicin, anidulafungin, immunoglobulins, gamma globulins, dronabinol, megestrol acetate, atovaquone, rifabutin, pentamidine, trimetrexate glucuronate, leucovorin, alitretinoin gel, erythropoietin, calcium hydroxyapatite, poly-L-lactic acid , somatropin rDNA, itraconazole, paclitaxel, voriconazole, cidofovir, fomivirsen, azithromycin, ruxolitinib, tocilizumab, bevirimat, TRIM5 alpha, Tat antagonist, trichosanthin, abzymes, calanolide A, ceragenin, cyanovirin-N, diarylpyrimidines, epigallocatechin gallate (EGCG), foscarnet, griffithsin, hydroxycarbamide, miltefosine, portmanteaus inhibitors, sitovirin, seliciclib, synergistic enhancers, tre recombinase, Zinc finger protein transcription factors, KP-1461, BIT225, aplaviroc, atevirdine, brecanavir, capravirine, dexelbucitabine, emivirine, lersivirine, rhodenosine, loviride, fomivirsen, glycyrrhizic acid (anti-inflammatory, inhibits 11beta-hydroxysteroid dehydrogenase), zinc salts, cellulose sulfate, cyclodextrin, dextrin-2-sulfate, NCP7 inhibitors, AMD-3100, BMS-806, BMS-793, C31G, carrageenan, CD4-IgG2, cellulose acetate phthalate,mAb 2G12, mAb b12, Merck167, plant lectin, polynaphthalene sulfate, polysulfo-styrene, PRO2000, PSC-Rantes, SCH-C, SCH-D, T-20, TMC-125, UC-781, UK-427, UK-857, Caraguard (PC-515), brincidofovir (CMX001), zidovudine, virus-specific cytotoxic T cells, idoxuridine, podophyllotoxin, rifampicin, methisazone, interferon alpha-2b (Intron-A), pegylated interferon alpha-2a, ribavirin, Moroxydine, pleconaril, BCX4430, taribavirin (viramidine, ICN3142), favipiravir, lintatolimod, ibasitabine (5-iodo-2'-deoxycytidine), methisazone, Amplgen, arbidol, Atripla®, Combivir, Immunovir, Nexavir, Trizivir, Truvada, lamivudine, dideoxyadenosine, floxuridine, idoxuridine, inosine pranobex, 2'-deoxyadenosine Oxy-5-(methylamino)uridine, digoxin, imiquimod, interferon type III, interferon type II, interferon type I, tea tree oil, glycyrrhizinic acid, fialuridine, telbivudine, adefovir, entecavir, lamivudine, clevudine, asunaprevir, boceprevir, faldaprevir, grazoprevir, paritaprevir, ritonavir, telaprevir, simeprevir, sofosbuvir, ACH-3102, daclatasvir, deleofvir, elbasvir, ledipasvir, MK-36 82, MK-8408, samatasvir, ombitasvir, entecavir, elderberry sambux, umifenovir, amantadine, rimantadine, oseltamivir, zanamivir, peramivir, laninamivir, pyrrole polyamide, lopinavir, or salts, solvates, and / or combinations thereof; and b) one or more of the following active agents: 17a-ethynyl-levonorgestrel-17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, ethinyl estradiol, levonorgestrel,The composition may comprise one or more of medroxyprogesterone acetate, nestrone, norethindrone, ethynodiol diacetate, RU486, N9, mifepristone, mifegin, mifeprex, 17a-ethynyl-levonorgestrel, 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, megestrol, etono-progestin alonegestrel, and 17-acetoxy-16-methylene-19-norprogesterone, or salts, solvates, or combinations thereof. In some embodiments, the composition is a pre-exposure composition comprising a low dose of one or more active agents. In some embodiments, the composition is a post-exposure composition comprising a high dose of one or more active agents. In some embodiments, the composition further prevents and / or treats HIV infection. In some embodiments, the composition is further administered with one or more HIV antivirals to prevent and / or treat HIV. In some embodiments, the composition further comprises or is administered with one or more additional contraceptive agents.

[0134] In some embodiments, the compositions useful in the methods described herein for preventing pregnancy and for preventing HSV infection in seronegative subjects comprise a) one or more of the following active agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoc one, two, three, four, five, or more of sudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or salts, solvates, or combinations thereof; b) the following active agents: maraviroc, enfuvirtide, vicriviroc, senic Riviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibody, DCM205, DARPins, caprine antibody, VIR-576, enfuvirtide (T-20), AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsin n), lectin, pentafuside, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, MK-0518, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoporoxil fumarate, zidovudine, apricitabine, stampidine,Elvucitabine, Rasivir, Amdoxovir, Stavudine, Zalcitabine, Festinavir, Dideoxycytidine (ddC), Azidothymidine, Tenofovir Alafenamide Fumarate, Entecavir, Delavirdine, Efavirenz, Etravirine (TMC-125), Nevirapine, Rilpivirine, Doravirine, Calanolide A, Capravirine, Epivir, Adefovir, Dapivirine, Lersivirine, Alovudine, Elvucitabine, TMC-278, DPC-083, Amdoxovir, (-)-beta-D-2,6-diamino- Purine dioxolane, MIV-210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC-278, KP1461, KP-1212, rhodenosine (FddA), 5-[(3,5-dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamate, (-)-I2-D-2,6-diaminopurine dioxolane, AVX-7 54, BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4-dihydro-4-trifluoromethyl-2(1H)-quinazolinone), TMC-120, L697639, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir (SC-52151), droxinavir, Emtriva, Invirase, Agenerase, TMC-126, Mozenavir one, two, three or four of droxinavir (DMP-450), JE-2147 (AG1776), L-756423, KNI-272, DPC-681, DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), or salts, solvates or combinations thereof;or more; and c) the active agents of: 17a-ethynyl-levonorgestrel-17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, ethinyl estradiol, levonorgestrel, medroxyprogesterone acetate, nestrone, norethindrone, ethynodiol diacetate, RU486, N9, mifepristone, mifegin, mifeprex, 17a-ethynyl-levonorgestrel. , 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, megestrol, etono-progestin alonegestrel, and 17-acetoxy-16-methylene-19-norprogesterone, or salts, solvates, or combinations thereof. In some embodiments, the composition is a pre-exposure composition comprising a low dose of one or more active agents. In some embodiments, the composition is a post-exposure composition comprising a high dose of one or more active agents. In some embodiments, the composition further prevents and / or treats HIV infection. In some embodiments, the composition is further administered with one or more HIV antivirals to prevent and / or treat HIV. In some embodiments, the composition further comprises or is administered in conjunction with one or more additional contraceptive agents.

[0135] In some embodiments, the compositions useful in the methods described herein for preventing pregnancy and treating HSV infection in seropositive subjects comprise a) one or more of the following active agents: valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulation (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoc one, two, three, four, five, or more of sudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or salts, solvates, or combinations thereof; b) the following active agents: maraviroc, enfuvirtide, vicriviroc, senic Riviroc, ibalizumab, fostemsavir (BMS-663068), ibalizumab (TMB-355, TNX-355), PRO140, b12 antibody, DCM205, DARPins, caprine antibody, VIR-576, enfuvirtide (T-20), AMD11070, PR0542, SCH-C, T-1249, cyanovirin, griffithsin n), lectin, pentafuside, dolutegravir, elvitegravir, raltegravir, globoidnan A, MK-2048, BI224436, cabotegravir, GSK1265744, GSK-572, MK-0518, abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, tenofovir disoporoxil fumarate, zidovudine, apricitabine, stampidine,Elvucitabine, Rasivir, Amdoxovir, Stavudine, Zalcitabine, Festinavir, Dideoxycytidine (ddC), Azidothymidine, Tenofovir Alafenamide Fumarate, Entecavir, Delavirdine, Efavirenz, Etravirine (TMC-125), Nevirapine, Rilpivirine, Doravirine, Calanolide A, Capravirine, Epivir, Adefovir, Dapivirine, Lersivirine, Alovudine, Elvucitabine, TMC-278, DPC-083, Amdoxovir, (-)-beta-D-2,6-diamino- Purine dioxolane, MIV-210 (FLG), DFC (dexelbucitabine), dioxolantimidine, L697639, atevirdine (U87201E), MIV-150, GSK-695634, GSK-678248, TMC-278, KP1461, KP-1212, rhodenosine (FddA), 5-[(3,5-dichlorophenyl)thio]-4-isopropyl-1-(4-pyridylmethyl)imidazole-2-methanolcarbamate, (-)-I2-D-2,6-diaminopurine dioxolane, AVX-754 , BCH-13520, BMS-56190 ((4S)-6-chloro-4-[(1E)-cyclopropylethenyl]-3,-4-dihydro-4-trifluoromethyl-2(1H)-quinazolinone), TMC-120, L697639, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, tipranavir, lopinavir, amprenavir, telinavir (SC-52151), droxinavir, Emtriva, Invirase, Agenerase, TMC-126, mozenavir ( DMP-450), JE-2147 (AG1776), L-756423, KNI-272, DPC-681, DPC-684, BMS186318, droxinavir (SC-55389a), DMP-323, KNI-227, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine, AG-1859, RO-033-4649, R-944, DMP-850, DMP-851, brecanavir (GW640385), or salts, solvates, or combinations thereof,or more; and c) the active agents of: 17a-ethynyl-levonorgestrel-17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, ethinylestradiol, levonorgestrel, medroxyprogesterone acetate, nestrone, norethindrone, ethynodiol diacetate, RU486, N9, mifepristone, mifegin, mifeprex, 17a-ethynyl-levonorgestrel

[0013] The composition may comprise one, two, three, four, or more of: 17b-hydroxy-estra-4,9,11-trien-3-one, estradiol, norgestrienone, progesterone, etonogestrel (3-keto-desogestrel), progestin, megestrol, etono-progestin alonegestrel, and 17-acetoxy-16-methylene-19-norprogesterone, or salts, solvates, or combinations thereof. In some embodiments, the composition is a pre-exposure composition comprising a low dose of one or more active agents. In some embodiments, the composition is a post-exposure composition comprising a high dose of one or more active agents. In some embodiments, the composition further prevents and / or treats HIV infection. In some embodiments, the composition is further administered with one or more HIV antivirals to prevent and / or treat HIV. In some embodiments, the composition further comprises or is administered in conjunction with one or more additional contraceptive agents.

[0136] Valacyclovir Compositions In various embodiments, provided herein are compositions useful for preventing HSV infection in HSV-seronegative subjects, the compositions comprising the active agent valacyclovir or a salt or solvate thereof, and further comprising and / or administered with one or more additional active agents. In various embodiments, provided herein are methods for preventing HSV infection in HSV-seronegative subjects, the methods comprising administering to the subject a combination of valacyclovir or a salt or solvate thereof and one or more additional active agents. In some cases, the combination of valacyclovir and one or more additional active agents further prevents one or more additional infectious diseases, such as infection by HIV. In some cases, the combination of valacyclovir and one or more additional active agents is administered together in one composition. In some cases, valacyclovir and one or more additional active agents are co-administered in different compositions. In some embodiments, at least one of the one or more additional active agents is an antiviral agent, such as an HSV antiviral agent, an HIV antiviral agent, and / or any antiviral agent described elsewhere herein. In some embodiments, at least one of the one or more additional active agents is a contraceptive. In some embodiments, at least one of the one or more additional active agents is an antiviral agent, and at least one of the one or more additional active agents is a contraceptive. In some cases, one or more active agents are administered to an HSV-seronegative subject before exposure to HSV to reduce the risk of acquiring HSV infection. In some cases, one or more active agents are administered to an HSV-seronegative subject after exposure to HSV to reduce the risk of acquiring HSV infection. In some cases, one or more active agents are administered to an HSV-seronegative subject before exposure to HSV, and one or more active agents are administered to an HSV-seronegative subject after exposure to HSV. In some of these cases, the dose of one or more active agents administered before exposure to HSV is different from the dose of one or more active agents administered after exposure to HSV.In some cases, contraceptives are administered to HSV-seronegative subjects before and / or after the subject engages in an activity that may result in pregnancy, such as an activity that results in exposure to HSV, to reduce the risk of pregnancy.In some embodiments, valacyclovir and / or one or more additional active agents are administered using an oral formulation, such as a pill, capsule, tablet, or liquid.In some embodiments, valacyclovir and / or one or more additional active agents are administered using a long-acting delivery device, such as an intravaginal ring.In some embodiments, the method for preventing HSV infection in HSV-seronegative subjects further includes administering one or more antiviral agents to the HSV-seropositive partner of the HSV-seronegative subject, for example, as suppressive therapy.In some cases, the HSV-seropositive partner is administered an HSV antiviral agent.

[0137] Examples of HSV antivirals include, but are not limited to, valacyclovir, acyclovir, famciclovir, pritelivir, penciclovir, ganciclovir, valganciclovir, cidofovir, foscarnet, darunavir, glycyrrhizinic acid, glutamine, FV-100, ASP2151, me-609, ASP2151, topical VDO, PEG formulations (Devirex AG), vidarabine, cidofovir, crofelemer (SP-303T), EPB-348, CMX001, V212, NB-001, squaric acid, ionic zinc, sorivudine (ARYS-01), trifluridine, 882C87, Merlin (ethanol and glycolic acid mixture), vitamin C, AIC316, versabase gel with Sarracenia purpurea, UB-621, lysine, edoxudine, brivudine, cytarabine, docosanol, tromantadine, resiquimod (R-848), imiquimod, resiquimod, tenofovir, tenofovir disoproxil fumarate, tenofovir alafenamide fumarate, or a salt, solvate, or combination thereof.

[0138] In some embodiments, a method for preventing HSV infection in an HSV-seronegative subject comprises administering to the HSV-seronegative subject about or at least about 200 mg, 250 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1150 mg, 1200 mg, 1250 mg, 1300 mg, 1350 mg, 1400 mg, 1450 mg, 1500 mg, 1550 mg, 1600 mg, 1700 mg, or 1800 mg of valacyclovir or a salt or solvate thereof. In some cases, valacyclovir or a salt or solvate thereof is administered at a dosage of about 500 mg to about 1500 mg, or about 500 mg to about 1000 mg. In some cases, valacyclovir or a salt or solvate thereof is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously (e.g., using a long-acting delivery device).

[0139] In some embodiments, a composition useful for preventing HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises emtricitabine. In some embodiments, a method for preventing HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof to the subject. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof to the HSV-seronegative subject. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once daily, twice daily, three times daily, four times daily, or continuously for a predetermined period of time. In some cases, a method for preventing HSV infection in an HSV-seronegative subject includes administering to the HSV-seronegative subject between about 500 mg and about 1500 mg of valacyclovir, or a salt or solvate thereof, and between about 100 mg and about 300 mg of emtricitabine, or a salt or solvate thereof.

[0140] In some embodiments, a composition useful for preventing HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises lamivudine. In some embodiments, a method for preventing HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering lamivudine or a salt or solvate thereof to the subject. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine or a salt or solvate thereof to the HSV-seronegative subject. In some cases, lamivudine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once daily, twice daily, three times daily, four times daily, or continuously for a predetermined period of time. In some cases, a method for preventing HSV infection in an HSV-seronegative subject includes administering to the HSV-seronegative subject between about 500 mg and about 1500 mg of valacyclovir, or a salt or solvate thereof, and between about 100 mg and about 300 mg of lamivudine, or a salt or solvate thereof.

[0141] In some embodiments, a composition useful for preventing HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises glycyrrhizic acid. In some embodiments, a method for preventing HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering glycyrrhizic acid or a salt or solvate thereof to the subject. In some embodiments, the method comprises administering at least or about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, or 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, or 20 mg of glycyrrhizic acid or a salt or solvate thereof to the HSV-seronegative subject. In some cases, glycyrrhizic acid is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, a method for preventing HSV infection in an HSV-seronegative subject includes administering to the HSV-seronegative subject between about 500 mg and about 1500 mg of valacyclovir, or a salt or solvate thereof, and between about 1 mg and about 10 mg of glycyrrhizinic acid, or a salt or solvate thereof.

[0142] In some embodiments, a composition useful for preventing HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises elderberry. In some embodiments, a method for preventing HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering elderberry or a salt or solvate thereof to the subject. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of elderberry or a salt or solvate thereof to the HSV-seronegative subject. In some cases, elderberry is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, a method for preventing HSV infection in an HSV-seronegative subject includes administering to the HSV-seronegative subject between about 500 mg and about 1500 mg of valacyclovir, or a salt or solvate thereof, and between about 100 mg and about 200 mg of elderberry, or a salt or solvate thereof.

[0143] In some embodiments, a composition useful for preventing HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises plitelivir. In some embodiments, a method for preventing HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering plitelivir or a salt or solvate thereof to the subject. In some embodiments, the method comprises administering at least or about 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 90 mg, or 100 mg of plitelivir or a salt or solvate thereof to an HSV-seronegative subject. In some cases, pritelivir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, a method for preventing HSV infection in an HSV-seronegative subject comprises administering to the HSV-seronegative subject between about 500 mg and about 1500 mg of valacyclovir or a salt or solvate thereof, and between about 5 mg and about 75 mg of pritelivir or a salt or solvate thereof.

[0144] In some embodiments, a composition useful for preventing HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises plitelivir and emtricitabine. In some embodiments, a method for preventing HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering plitelivir or a salt or solvate thereof and emtricitabine or a salt or solvate thereof to the subject. In some embodiments, the method comprises administering at least or about 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 90 mg, or 100 mg of plitelivir or a salt or solvate thereof to an HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine, or a salt or solvate thereof. In some cases, plitelivir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some instances, a method for preventing HSV infection in an HSV-seronegative subject includes administering to the HSV-seronegative subject between about 500 mg and about 1500 mg of valacyclovir or a salt or solvate thereof, between about 5 mg and about 75 mg of plitelivir or a salt or solvate thereof, and between about 100 mg and about 300 mg of emtricitabine or a salt or solvate thereof.

[0145] In some embodiments, a composition useful for preventing HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises plitelivir and lamivudine. In some embodiments, a method for preventing HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering plitelivir or a salt or solvate thereof and lamivudine or a salt or solvate thereof to the subject. In some embodiments, the method comprises administering at least or about 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 90 mg, or 100 mg of plitelivir or a salt or solvate thereof to an HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine, or a salt or solvate thereof. In some cases, plitelivir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, lamivudine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some instances, a method for preventing HSV infection in an HSV-seronegative subject includes administering to the HSV-seronegative subject between about 500 mg and about 1500 mg of valacyclovir or a salt or solvate thereof, between about 5 mg and about 75 mg of plitelivir or a salt or solvate thereof, and between about 100 mg and about 300 mg of lamivudine or a salt or solvate thereof.

[0146] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises emtricitabine and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof and one or more contraceptives to the subject. In some cases, the contraceptives comprise levonorgestrel and ethinyl estradiol. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof to the HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, or 0.2 mg of levonorgestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once daily, twice daily, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, levonorgestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of levonorgestrel and ethinyl estradiol, followed by 7 days of placebo.In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; and c) administering to the subject about 0.05 mg to about 0.2 mg of levonorgestrel or a salt or solvate thereof, and about 0.01 mg to about 0.03 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0147] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises lamivudine and one or more contraceptive agents. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering lamivudine or a salt or solvate thereof and one or more contraceptive agents to the subject. In some cases, the contraceptive agents comprise levonorgestrel and ethinyl estradiol. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine or a salt or solvate thereof to the HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, or 0.2 mg of levonorgestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, lamivudine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once daily, twice daily, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, levonorgestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of levonorgestrel and ethinyl estradiol, followed by 7 days of placebo.In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 100 mg to about 300 mg of lamivudine or a salt or solvate thereof once daily; and c) administering to the subject about 0.05 mg to about 0.2 mg of levonorgestrel or a salt or solvate thereof, and about 0.01 mg to about 0.03 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0148] In some embodiments, the composition useful for preventing pregnancy and HSV infection in seronegative subjects, comprising valacyclovir or its salt or solvate, further comprises glycyrrhizic acid and one or more contraceptives. In some embodiments, the method for preventing pregnancy and HSV infection in seronegative subjects, comprising administering valacyclovir or its salt or solvate to the subject, further comprises administering glycyrrhizic acid or its salt or solvate and one or more contraceptives to the subject. In some cases, the contraceptives comprise levonorgestrel and ethinyl estradiol. In some embodiments, the method comprises administering at least or about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, or 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, or 20 mg of glycyrrhizic acid or its salt or solvate to the HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, or 0.2 mg of levonorgestrel, or a salt or solvate thereof.In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinylestradiol, or a salt or solvate thereof.In some cases, glycyrrhizic acid is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, levonorgestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of levonorgestrel and ethinyl estradiol, followed by 7 days of placebo.In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 1 mg to about 10 mg of glycyrrhizinic acid or a salt or solvate thereof once daily; and c) administering to the subject about 0.05 mg to about 0.2 mg of levonorgestrel or a salt or solvate thereof, and about 0.01 mg to about 0.03 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0149] In some embodiments, the composition useful for preventing pregnancy and HSV infection in seronegative subjects, comprising valacyclovir or its salt or solvate, further comprises elderberry and one or more contraceptives. In some embodiments, the method for preventing pregnancy and HSV infection in seronegative subjects, comprising administering valacyclovir or its salt or solvate to the subject, further comprises administering elderberry or its salt or solvate and one or more contraceptives to the subject. In some cases, the contraceptives comprise levonorgestrel and ethinylestradiol. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of elderberry or its salt or solvate to the HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, or 0.2 mg of levonorgestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, elderberry is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, levonorgestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of levonorgestrel and ethinyl estradiol, followed by 7 days of placebo.In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 100 mg to about 200 mg of elderberry or a salt or solvate thereof once daily; and c) administering to the subject about 0.05 mg to about 0.2 mg of levonorgestrel or a salt or solvate thereof, and about 0.01 mg to about 0.03 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0150] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises emtricitabine, tenofovir, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives to the subject. In some cases, the contraceptives comprise levonorgestrel and ethinyl estradiol. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof to an HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, or 0.2 mg of levonorgestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time.In some cases, levonorgestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of levonorgestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; and d) administering to the subject about 0.05 mg to about 0.2 mg of levonorgestrel or a salt or solvate thereof, and about 0.01 mg to about 0.03 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0151] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises lamivudine, tenofovir, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering lamivudine or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives to the subject. In some cases, the contraceptives comprise levonorgestrel and ethinyl estradiol. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine or a salt or solvate thereof to the HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, or 0.2 mg of levonorgestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, lamivudine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time.In some cases, levonorgestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of levonorgestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 100 mg to about 300 mg of lamivudine or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; and d) administering to the subject about 0.05 mg to about 0.2 mg of levonorgestrel or a salt or solvate thereof, and about 0.01 mg to about 0.03 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0152] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises glycyrrhizic acid, tenofovir, emtricitabine, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering glycyrrhizic acid or a salt or solvate thereof, emtricitabine or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives to the subject. In some cases, the contraceptives comprise levonorgestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, or 20 mg of glycyrrhizinic acid or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, or 0.2 mg of levonorgestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof.In some cases, glycyrrhizinic acid is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, levonorgestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of levonorgestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 1 mg to about 10 mg of glycyrrhizinic acid or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; and e) administering to the subject about 0.05 mg to about 0.2 mg of levonorgestrel or a salt or solvate thereof, and about 0.01 mg to about 0.03 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0153] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises elderberry, tenofovir, emtricitabine, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering elderberry or a salt or solvate thereof, emtricitabine or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives to the subject. In some cases, the contraceptives comprise levonorgestrel and ethinyl estradiol. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of elderberry or a salt or solvate thereof to an HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, or 0.2 mg of levonorgestrel or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, the elderberry is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time.In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, levonorgestrel and ethinyl estradiol are administered in cycles, each cycle comprising 21 days of daily administration of levonorgestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 50 mg to about 200 mg of elderberry or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; and e) administering to the subject about 0.05 mg to about 0.2 mg of levonorgestrel or a salt or solvate thereof, and about 0.01 mg to about 0.03 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0154] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises tenofovir, emtricitabine, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives to the subject. In some cases, the contraceptives comprise desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof to an HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of desogestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time.In some cases, dosogestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of dosogestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; and d) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0155] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises tenofovir, lamivudine, and one or more contraceptive agents. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering lamivudine or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptive agents to the subject. In some cases, the contraceptive agents include desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof to an HSV-seronegative subject. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of desogestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, lamivudine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time.In some cases, dosogestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of dosogestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 100 mg to about 300 mg of lamivudine or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; and d) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0156] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises tenofovir, emtricitabine, glycyrrhizic acid, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering to the subject emtricitabine or a salt or solvate thereof, glycyrrhizic acid or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives. In some cases, the contraceptives comprise desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, or 20 mg of glycyrrhizic acid, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of desogestrel, or a salt or solvate thereof. In some embodiments, the methods comprise administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof.In some cases, glycyrrhizinic acid is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, dosogestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of dosogestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 1 mg to about 10 mg of glycyrrhizinic acid or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; and e) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0157] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject comprising valacyclovir or a salt or solvate thereof further comprises tenofovir, emtricitabine, elderberry, and one or more contraceptive agents. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof, elderberry or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptive agents to the subject. In some cases, the contraceptive agents include desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of elderberry or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of dosogestrel, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof.In some cases, Sambucus nigra is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, Emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, Tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, dosogestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of dosogestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 50 mg to about 200 mg of elderberry or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; and e) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0158] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises tenofovir, emtricitabine, efavirenz, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering to the subject emtricitabine or a salt or solvate thereof, efavirenz or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives. In some cases, the contraceptives comprise desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, or 800 mg of efavirenz, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of desogestrel, or a salt or solvate thereof. In some embodiments, the methods comprise administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof.In some cases, efavirenz is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, dosogestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of dosogestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 400 mg to about 700 mg of efavirenz or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; and e) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0159] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises tenofovir, lamivudine, efavirenz, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering to the subject lamivudine or a salt or solvate thereof, efavirenz or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives. In some cases, the contraceptives comprise desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, or 800 mg of efavirenz, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of desogestrel, or a salt or solvate thereof. In some embodiments, the methods comprise administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof.In some cases, efavirenz is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, lamivudine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, dosogestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of dosogestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 400 mg to about 700 mg of efavirenz or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of lamivudine or a salt or solvate thereof once daily; and e) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0160] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject comprising valacyclovir or a salt or solvate thereof further comprises tenofovir, emtricitabine, efavirenz, glycyrrhizic acid, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof, efavirenz or a salt or solvate thereof, tenofovir or a salt or solvate thereof, glycyrrhizic acid or a salt or solvate thereof, and one or more contraceptives to the subject. In some cases, the contraceptives comprise desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, or 800 mg of efavirenz or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, or 20 mg of glycyrrhizinic acid or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of dosogestrel or a salt or solvate thereof.In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, efavirenz is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, glycyrrhizic acid is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, desogestrel and ethinyl estradiol are administered in cycles, each cycle comprising 21 days of daily administration of desogestrel and ethinyl estradiol, followed by 7 days of placebo.In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 400 mg to about 700 mg of efavirenz or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of emtricitabine or e) administering to the subject about 1 mg to about 10 mg of glycyrrhizinic acid or a salt or solvate thereof once daily; and f) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0161] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises tenofovir, emtricitabine, efavirenz, elderberry, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof, efavirenz or a salt or solvate thereof, tenofovir or a salt or solvate thereof, elderberry or a salt or solvate thereof, and one or more contraceptives to the subject. In some cases, the contraceptives comprise desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, or 800 mg of efavirenz or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of elderberry, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of dosogestrel, or a salt or solvate thereof.In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, efavirenz is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, elderberry is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, desogestrel and ethinyl estradiol are administered in cycles, each cycle comprising 21 days of daily administration of desogestrel and ethinyl estradiol, followed by 7 days of placebo.In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 400 mg to about 700 mg of efavirenz or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of emtricitabine or e) administering to the subject about 50 mg to about 300 mg of elderberry or a salt or solvate thereof once daily; and f) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0162] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises tenofovir, emtricitabine, dolutegravir, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering to the subject emtricitabine or a salt or solvate thereof, dolutegravir or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives. In some cases, the contraceptives comprise desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of dolutegravir, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of desogestrel, or a salt or solvate thereof. In some embodiments, the methods comprise administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof.In some cases, dolutegravir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, dosogestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of dosogestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 20 mg to about 70 mg of dolutegravir or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of emtricitabine or a salt or solvate thereof once daily; and e) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0163] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject, comprising valacyclovir or a salt or solvate thereof, further comprises tenofovir, lamivudine, dolutegravir, and one or more contraceptives. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering to the subject lamivudine or a salt or solvate thereof, dolutegravir or a salt or solvate thereof, tenofovir or a salt or solvate thereof, and one or more contraceptives. In some cases, the contraceptives comprise desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of dolutegravir, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of desogestrel, or a salt or solvate thereof. In some embodiments, the methods comprise administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof.In some cases, dolutegravir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, lamivudine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, dosogestrel and ethinyl estradiol are administered in cycles, with each cycle comprising 21 days of daily administration of dosogestrel and ethinyl estradiol, followed by 7 days of placebo. In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 20 mg to about 70 mg of dolutegravir or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of lamivudine or a salt or solvate thereof once daily; and e) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0164] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject comprising valacyclovir or a salt or solvate thereof further comprises tenofovir, emtricitabine, dolutegravir, glycyrrhizic acid, and one or more contraceptive agents. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof, dolutegravir or a salt or solvate thereof, tenofovir or a salt or solvate thereof, glycyrrhizic acid or a salt or solvate thereof, and one or more contraceptive agents to the subject. In some cases, the contraceptive agents include desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of dolutegravir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, or 20 mg of glycyrrhizinic acid or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of dosogestrel or a salt or solvate thereof.In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, dolutegravir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, glycyrrhizic acid is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, desogestrel and ethinyl estradiol are administered in cycles, each cycle comprising 21 days of daily administration of desogestrel and ethinyl estradiol, followed by 7 days of placebo.In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir or a salt or solvate thereof once daily; b) administering to the subject about 20 mg to about 70 mg of dolutegravir or a salt or solvate thereof once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir or a salt or solvate thereof once daily; d) administering to the subject about 100 mg to about 300 mg of emtricitabine or e) administering to the subject about 1 mg to about 10 mg of glycyrrhizinic acid or a salt or solvate thereof once daily; and f) administering to the subject about 0.05 mg to about 0.2 mg of desogestrel or a salt or solvate thereof, and about 0.02 mg to about 0.04 mg of ethinyl estradiol or a salt or solvate thereof once daily for about 21 days, followed by a placebo for about 7 days.

[0165] In some embodiments, a composition useful for preventing pregnancy and HSV infection in a seronegative subject comprising valacyclovir or a salt or solvate thereof further comprises tenofovir, emtricitabine, dolutegravir, sambucus nigra, and one or more contraceptive agents. In some embodiments, a method for preventing pregnancy and HSV infection in a seronegative subject, comprising administering valacyclovir or a salt or solvate thereof to the subject, further comprises administering emtricitabine or a salt or solvate thereof, dolutegravir or a salt or solvate thereof, tenofovir or a salt or solvate thereof, sambucus nigra or a salt or solvate thereof, and one or more contraceptive agents to the subject. In some cases, the contraceptive agents include desogestrel and ethinyl estradiol. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of tenofovir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of emtricitabine or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of dolutegravir or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 50 mg, 100 mg, 10 mg, 200 mg, 250 mg, or 300 mg of elderberry, or a salt or solvate thereof. In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.05 mg, 0.10 mg, 0.15 mg, 0.2 mg, 0.25 mg, or 0.3 mg of dosogestrel, or a salt or solvate thereof.In some embodiments, the method comprises administering to an HSV-seronegative subject at least or about 0.01 mg, 0.015 mg, 0.02 mg, 0.025 mg, 0.03 mg, 0.035 mg, or 0.04 mg of ethinyl estradiol, or a salt or solvate thereof. In some cases, dolutegravir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, emtricitabine is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, tenofovir is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, elderberry is administered once a week, twice a week, three times a week, four times a week, five times a week, six times a week, once a day, twice a day, three times a day, four times a day, or continuously for a predetermined period of time. In some cases, desogestrel and ethinyl estradiol are administered in cycles, each cycle comprising 21 days of daily administration of desogestrel and ethinyl estradiol, followed by 7 days of placebo.In some instances, a method for preventing pregnancy and HSV infection in an HSV-seronegative subject includes: a) administering to the subject about 500 to about 1500 mg of valacyclovir, or a salt or solvate thereof, once daily; b) administering to the subject about 20 mg to about 70 mg of dolutegravir, or a salt or solvate thereof, once daily; c) administering to the subject about 100 mg to about 400 mg of tenofovir, or a salt or solvate thereof, once daily; d) administering to the subject about 100 mg to about 300 mg of emtricitabine or its salt or solvate; once daily for about 21 days, followed by a placebo for about 7 days.

[0166] Non-limiting antiviral compositions for preventing HSV infection In some embodiments, provided herein are methods for preventing HSV infection in an HSV-seronegative subject, comprising administering to the subject about 200 mg to about 2,500 mg of valacyclovir, or a salt or solvate thereof, once daily. In some cases, valacyclovir is administered before exposure to HSV. In some cases, valacyclovir is administered after exposure to HSV. In some cases, valacyclovir is administered both before and after exposure to HSV. In some cases, valacyclovir is administered in conjunction with one or more additional active agents, e.g., one or more additional antiviral agents, one or more contraceptive agents, or one or more additional antiviral agents and one or more contraceptive agents. In some embodiments, the method further prevents infection with one or more additional infectious diseases, e.g., HIV. In some embodiments in which one or more contraceptive agents are further administered to an HSV-seronegative subject, the method further prevents pregnancy. In some embodiments, the method further includes administering to the HSV-seropositive partner of the HSV-seronegative subject one or more antiviral agents, e.g., one or more HSV antiviral agents, one or more HIV antiviral agents, and / or any antiviral agent described herein. In some cases, the method includes administering to the HSV-seronegative subject about 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, or 2500 mg of valacyclovir, or a salt or solvate thereof, once daily. In some instances, the method comprises administering to the HSV-seronegative subject about 400 mg to about 2000 mg, about 400 mg to about 1000 mg, or about 1000 mg to about 2000 mg of valacyclovir, or a salt or solvate thereof, once daily.In some embodiments, the additional antiviral agents include tenofovir, emtricitabine, lamivudine, efavirenz, raltegravir, dolutegravir, maravoric, rilpirivine, Atripla®, and salts, solvates, and / or combinations thereof. In some embodiments, one of the one or more additional antiviral agents is tenofovir, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 500 mg of tenofovir once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, or 500 mg of tenofovir per day. In some embodiments, one of the one or more additional antiviral agents is emtricitabine, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 300 mg of emtricitabine once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of emtricitabine per day. In some embodiments, one of the one or more additional antiviral agents is lamivudine, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 400 mg of lamivudine once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine per day. In some embodiments, one of the one or more additional antiviral agents is efavirenz, and the method further comprises administering to the HSV-seronegative subject about 300 mg to about 900 mg of efavirenz once daily, e.g., about 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, or 900 mg of efavirenz per day. In some embodiments, one of the one or more additional antiviral agents is raltegravir, and the method further comprises administering to the HSV-seronegative subject about 200 mg to about 600 mg of raltegravir twice daily, e.g., about 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg of raltegravir twice daily.In some embodiments, one of the one or more additional antiviral agents is dolutegravir, and the method further comprises administering to the HSV-seronegative subject about 10 mg to about 100 mg of dolutegravir once daily, e.g., about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of dolutegravir per day. In some embodiments, one of the one or more additional antiviral agents is maraviroc, and the method further comprises administering to the HSV-seronegative subject about 100 mg to about 400 mg of maraviroc twice daily, e.g., about 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of maraviroc twice daily. In some embodiments, one of the one or more additional antiviral agents is rilpivirine, and the method further includes administering to the HSV-seronegative subject about 10 mg to about 50 mg of rilpivirine once daily, e.g., about 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, or 50 mg of rilpivirine per day.In some embodiments, a) one of the one or more additional antiviral agents is emtricitabine, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 300 mg of emtricitabine once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of emtricitabine per day; b) one of the one or more additional antiviral agents is efavirenz, and the method further comprises administering to the HSV-seronegative subject about 300 mg to about 900 mg of efavirenz once daily, and c) one of the one or more additional antiviral agents is tenofovir, the method further comprising administering to the HSV-seronegative subject about 50 mg to about 500 mg of tenofovir once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, or 500 mg of tenofovir per day. In some cases, the one or more additional antiviral agents are administered before, after, or both before and after the HSV-seronegative subject is exposed to HSV. In some embodiments, the contraceptive comprises levonorgestrel, estradiol, desogestrel, ethinyl estradiol, norethindrone acetate, norgestimate, or a salt, solvate, or combination thereof. In some cases, the contraceptive comprises levonorgestrel and estradiol, and the method further comprises administering to the HSV-seronegative subject about 0.10 mg of levonorgestrel and about 0.02 mg of estradiol. In some cases, the contraceptive comprises desogestrel and ethinyl estradiol, and the method further comprises administering to the HSV-seronegative subject about 0.15 mg of desogestrel and about 0.03 mg of ethinyl estradiol.In some cases, the contraceptive comprises norethindrone acetate and ethinyl estradiol, and the method further comprises administering to the HSV-seronegative subject about 1 mg of norethindrone acetate and about 20 μg of ethinyl estradiol.In some cases, the contraceptive comprises norgestimate and ethinyl estradiol, and the method further comprises administering to the HSV-seronegative subject about 0.18 mg or about 0.25 mg of norgestimate and about 35 μg or about 25 μg of ethinyl estradiol.In some embodiments, the contraceptive is administered before, after, or both before and after the subject is exposed to HSV. In some cases, the contraceptive comprises levonorgestrel, and the method further comprises administering to the HSV-seronegative subject about 0.75 mg of levonorgestrel, wherein the 0.75 mg of levonorgestrel is administered to the subject once daily for two days after sexual activity that could result in conception. In some cases, one or more of the contraceptive agents are sold over the counter for subjects older than 14, 15, 16, 17, or 18 years of age.

[0167] In some embodiments, provided herein are methods for preventing HSV infection in an HSV-seronegative subject, comprising administering to the subject about 200 mg to about 2,000 mg of acyclovir, or a salt or solvate thereof, twice daily. In some cases, the acyclovir is administered before exposure to HSV. In some cases, the acyclovir is administered after exposure to HSV. In some cases, the acyclovir is administered both before and after exposure to HSV. In some cases, the acyclovir is administered in conjunction with one or more additional active agents, for example, in conjunction with one or more additional antiviral agents, in conjunction with one or more contraceptive agents, or in conjunction with one or more additional antiviral agents and one or more contraceptive agents. In some embodiments, the method further prevents infection with one or more additional infectious diseases, such as HIV. In some embodiments in which the HSV-seronegative subject is further administered one or more contraceptive agents, the method further prevents pregnancy. In some embodiments, the method further comprises administering to the HSV-seropositive partner of the HSV-seronegative subject one or more antiviral agents, e.g., one or more HSV antiviral agents, one or more HIV antiviral agents, and / or any antiviral agent described herein. In some embodiments, the method comprises administering to the HSV-seronegative subject about 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, or 1600 mg of acyclovir, or a salt or solvate thereof, twice daily. In some instances, the method comprises administering to the HSV-seronegative subject about 400 mg to about 800 mg, about 800 mg to about 1000 mg, or about 1000 mg to about 1600 mg of acyclovir, or a salt or solvate thereof, twice daily. In some embodiments, the additional antiviral agents include tenofovir, emtricitabine, lamivudine, efavirenz, raltegravir, dolutegravir, maravoric, rilpirivine, Atripla®, and salts, solvates, and / or combinations thereof.In some embodiments, one of the one or more additional antiviral agents is tenofovir, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 500 mg of tenofovir once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, or 500 mg of tenofovir per day. In some embodiments, one of the one or more additional antiviral agents is emtricitabine, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 300 mg of emtricitabine once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of emtricitabine per day. In some embodiments, one of the one or more additional antiviral agents is lamivudine, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 400 mg of lamivudine once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine per day. In some embodiments, one of the one or more additional antiviral agents is efavirenz, and the method further comprises administering to the HSV-seronegative subject about 300 mg to about 900 mg of efavirenz once daily, e.g., about 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, or 900 mg of efavirenz per day. In some embodiments, one of the one or more additional antiviral agents is raltegravir, and the method further comprises administering to the HSV-seronegative subject about 200 mg to about 600 mg of raltegravir twice daily, e.g., about 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg of raltegravir twice daily. In some embodiments, one of the one or more additional antiviral agents is dolutegravir, and the method further comprises administering to the HSV-seronegative subject about 10 mg to about 100 mg of dolutegravir once daily, e.g., about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of dolutegravir per day.In some embodiments, one of the one or more additional antiviral agents is maraviroc, and the method further comprises administering to the HSV-seronegative subject about 100 mg to about 400 mg of maraviroc twice daily, e.g., about 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of maraviroc twice daily. In some embodiments, one of the one or more additional antiviral agents is rilpivirine, and the method further comprises administering to the HSV-seronegative subject about 10 mg to about 50 mg of rilpivirine once daily, e.g., about 10 mg, 20 mg, 25 mg, 30 mg, 40 mg, or 50 mg of rilpivirine per day. In some embodiments, a) one of the one or more additional antiviral agents is emtricitabine, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 300 mg of emtricitabine once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of emtricitabine per day; b) one of the one or more additional antiviral agents is efavirenz, and the method further comprises administering to the HSV-seronegative subject about 300 mg to about 900 mg of efavirenz once daily, and c) one of the one or more additional antiviral agents is tenofovir, the method further comprising administering to the HSV-seronegative subject about 50 mg to about 500 mg of tenofovir once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, or 500 mg of tenofovir per day. In some cases, the one or more additional antiviral agents are administered before, after, or both before and after exposure of the HSV-seronegative subject to HSV.In some embodiments, the contraceptive comprises levonorgestrel, estradiol, desogestrel, ethinyl estradiol, norethindrone acetate, norgestimate, or a salt, solvate, or combination thereof. In some cases, the contraceptive comprises levonorgestrel and estradiol, and the method further comprises administering to the HSV-seronegative subject about 0.10 mg of levonorgestrel and about 0.02 mg of estradiol. In some cases, the contraceptive comprises desogestrel and ethinyl estradiol, and the method further comprises administering to the HSV-seronegative subject about 0.15 mg of desogestrel and about 0.03 mg of ethinyl estradiol. In some cases, the contraceptive comprises norethindrone acetate and ethinyl estradiol, and the method further comprises administering about 1 mg of norethindrone acetate and about 20 μg of ethinyl estradiol to the HSV-seronegative subject.In some cases, the contraceptive comprises norgestimate and ethinyl estradiol, and the method further comprises administering about 0.18 mg or about 0.25 mg of norgestimate and about 35 μg or about 25 μg of ethinyl estradiol to the HSV-seronegative subject.In some embodiments, the contraceptive is administered before, after, or both before and after the subject is exposed to HSV.In some cases, the contraceptive comprises levonorgestrel, and the method further comprises administering about 0.75 mg of levonorgestrel to the HSV-seronegative subject, and the 0.75 mg of levonorgestrel is administered to the subject once a day for two days after sexual activity that can result in pregnancy. In some cases, one or more of the contraceptive agents are sold over the counter to subjects older than 14, 15, 16, 17, or 18 years of age.

[0168] In some embodiments, provided herein are methods for preventing HSV infection in an HSV-seronegative subject, comprising administering to the subject about 5 mg to about 80 mg of plitelivir, or a salt or solvate thereof, once daily. In some cases, plitelivir is administered before exposure to HSV. In some cases, plitelivir is administered after exposure to HSV. In some cases, plitelivir is administered both before and after exposure to HSV. In some cases, plitelivir is administered in conjunction with one or more additional active agents, for example, in conjunction with one or more additional antiviral agents, one or more contraceptive agents, or one or more additional antiviral agents and one or more contraceptive agents. In some embodiments, the method further prevents infection with one or more additional infectious diseases, such as HIV. In some embodiments in which one or more contraceptive agents are further administered to an HSV-seronegative subject, the method further prevents pregnancy. In some embodiments, the method further comprises administering to the HSV-seropositive partner of the HSV-seronegative subject one or more antiviral agents, e.g., one or more HSV antiviral agents, one or more HIV antiviral agents, and / or any antiviral agent described herein. In some embodiments, the method comprises administering to the HSV-seronegative subject about 5 mg, 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, or 80 mg of plitelivir, or a salt or solvate thereof, once daily. In some instances, the method comprises administering to the HSV-seronegative subject about 5 mg to about 20 mg, about 20 mg to about 50 mg, or about 50 mg to about 80 mg of plitelivir, or a salt or solvate thereof, once daily. In some embodiments, the additional antiviral agents include tenofovir, emtricitabine, lamivudine, efavirenz, raltegravir, dolutegravir, maravoric, rilpirivine, Atripla®, and salts, solvates, and / or combinations thereof.In some embodiments, one of the one or more additional antiviral agents is tenofovir, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 500 mg of tenofovir once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, or 500 mg of tenofovir per day. In some embodiments, one of the one or more additional antiviral agents is emtricitabine, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 300 mg of emtricitabine once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg of emtricitabine per day. In some embodiments, one of the one or more additional antiviral agents is lamivudine, and the method further comprises administering to the HSV-seronegative subject about 50 mg to about 400 mg of lamivudine once daily, e.g., about 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of lamivudine per day. In some embodiments, one of the one or more additional antiviral agents is efavirenz, and the method further comprises administering to the HSV-seronegative subject about 300 mg to about 900 mg of efavirenz once daily, e.g., about 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, or 900 mg of efavirenz per day. In some embodiments, one of the one or more additional antiviral agents is raltegravir, and the method further comprises administering to the HSV-seronegative subject about 200 mg to about 600 mg of raltegravir twice daily, e.g., about 200 mg, 300 mg, 400 mg, 500 mg, or 600 mg of raltegravir twice daily. In some embodiments, one of the one or more additional antiviral agents is dolutegravir, and the method further comprises administering to the HSV-seronegative subject about 10 mg to about 100 mg of dolutegravir once daily, e.g., about 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, or 100 mg of dolutegravir per day.In some embodiments, one of the one or more additional antiviral agents is maraviroc, and the method further comprises administering to the HSV-seronegative subject about 100 mg to about 400 mg of maraviroc twice daily, e.g., about 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, or 400 mg of maraviroc twice daily. In some embodiments, one of the o...

Claims

1. 1. A pharmaceutical composition for treating herpes simplex virus (HSV) infection or an HSV-related disease, for preventing HSV infection or an HSV-related disease, or for pre-exposure prophylaxis of HSV infection or an HSV-related disease in a subject, comprising a therapeutically effective amount of (a) valacyclovir, or a salt or solvate thereof, and (b) famciclovir, or a salt or solvate thereof, and optionally a pharma- ceutical acceptable excipient, diluent, carrier, and / or adjuvant, wherein the HSV-related disease comprises Alzheimer's disease, senile dementia, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, type 1 diabetes, SH2D1A / SAP deficiency, ITK deficiency, or MAGT1 deficiency.

2. 2. The pharmaceutical composition of claim 1, comprising 0.5 mg / kg to about 1000 mg / kg of body weight of (a) and 0.5 mg / kg to about 1000 mg / kg of body weight of (b).

3. 3. The pharmaceutical composition of claim 2, comprising a dosage ratio of (a) and (b) of about 5:1, about 4:1, about 3:1, about 2:1, about 1:1, about 1:2, about 1:3, about 1:4, or about 1:5 mg / kg.

4. A pharmaceutical composition for treating herpes simplex virus (HSV) infection, for preventing HSV infection, or for pre-exposure prophylaxis of HSV infection in a subject, comprising a therapeutically effective amount of an antiviral agent greater than 100 mg / kg body weight comprising acyclovir or a salt or solvate thereof, or valacyclovir or a salt or solvate thereof, or famciclovir or a salt or solvate thereof, or a combination thereof, thereby reducing the risk of HSV infection in said subject.

5. 5. The pharmaceutical composition of claim 4, comprising from 0.5 mg / kg to about 1000 mg / kg of body weight of the second antiviral agent.

6. 6. A pharmaceutical composition according to claim 4 or 5, comprising more than 100 mg / kg of body weight of valacyclovir and more than 100 mg / kg of body weight of famciclovir.

7. 7. The pharmaceutical composition according to any one of claims 1 to 6, comprising from about 1 mg to about 8000 mg of valacyclovir or a salt or solvate thereof and from about 1 mg to about 8000 mg of famciclovir or a salt or solvate thereof.

8. The pharmaceutical composition according to any one of claims 1 to 7, which is formulated for oral or parenteral administration.

9. The pharmaceutical composition of any one of claims 1 to 8, formulated for once-daily or twice-daily administration.

10. The pharmaceutical composition according to any one of claims 1 to 9, which is formulated in a sustained release form.

11. The pharmaceutical composition of any one of claims 1 to 10, further comprising a therapeutically effective amount of an HIV antiviral agent.

12. 12. The pharmaceutical composition of any one of claims 1 to 11, formulated for females and further comprising a therapeutically effective amount of a contraceptive.

13. The pharmaceutical composition of any one of claims 1 to 12, further comprising a therapeutically effective amount of an additional antiviral agent.

14. The pharmaceutical composition according to any one of claims 1 to 13, wherein the HSV is HSV-1.

15. The pharmaceutical composition described in any one of claims 1 to 13, wherein the HSV is HSV-2.

16. The pharmaceutical composition according to any one of claims 1 to 15, wherein the HSV infection is a neonatal infection.

17. The pharmaceutical composition described in any one of claims 1 to 16, wherein the HSV-related disease includes Alzheimer's disease.

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